profiling-luminal-ph-three-dimensional-gastrointestinal-organoids

Profiling Luminal pH in Three-Dimensional Gastrointestinal Organoids Using Microelectrodes

The optimization and detailed characterization of gastrointestinal organoid models require advanced methods for analyzing their luminal environments. This ...

Boston University

&#x80C3;&#x9ECF;&#x6DB2;&#x662F;&#x5DF2;&#x77E5;&#x7ECF;&#x8FC7;&#x5BF9;&#x54FA;&#x4E73;&#x52A8;&#x7269;&#x7684;&#x80C3;&#x7684;&#x80C3;&#x7C98;&#x6DB2;&#x5C42;&#x7684;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x662F;&#x81F3;&#x5173;&#x91CD;&#x8981;&#x7684; pH &#x4F9D;&#x8D56;&#x578B;&#x6EB6;&#x80F6;-&#x51DD;&#x80F6;&#x8F6C;&#x7CD6;&#x86CB;&#x767D;&#x3002;&#x6211;&#x4EEC;&#x63D0;&#x51FA;&#x57FA;&#x4E8E;&#x663E;&#x5FAE;&#x955C;&#x7684;&#x52A8;&#x6001;&#x5149;&#x6563;&#x5C04;&#x6570;&#x636E;&#x5BF9;&#x732A;&#x80C3;&#x9ECF;&#x5728; ph &#x503C; 6 &#xFF08;&#x89E3;&#x51B3;&#x65B9;&#x6848;&#xFF09; &#x548C; ph &#x503C; 2 (&#x556B;&#x55B1;) &#x4E0E;&#x793A;&#x8E2A;&#x7C92;&#x5B50;&#x7684;&#x5B58;&#x5728;&#x3002;&#x6570;&#x636E;&#x63D0;&#x4F9B;&#x7684;&#x5FAE;&#x578B;&#x7C98;&#x5EA6;&#x548C;&#x526A;&#x5207;&#x5F39;&#x6027;&#x6A21;&#x91CF;&#x7684;&#x6D4B;&#x91CF;&#x4EE5;&#x53CA;&#x5728; ph &#x503C; 2 &#x7684;&#x51DD;&#x80F6;&#x7684;&#x7F51;&#x683C;&#x5927;&#x5C0F;&#x7684;&#x4F30;&#x8BA1;&#x3002;&#x6211;&#x4EEC;&#x89C2;&#x5BDF;&#x51DD;&#x80F6;&#x4E2D;&#x7684;&#x5FAE;&#x578B;&#x7C98;&#x5EA6;&#x7EA6; 100 &#x500D;&#x4F4E;&#x4E8E;&#x5176;&#x5B8F;&#x89C2;&#x7C98;&#x5EA6;&#xFF0C;&#x6697;&#x793A;&#x5927;&#x6BDB;&#x5B54;&#x5F00;&#x653E;&#x51CF;&#x5C11;&#x6469;&#x64E6;&#x4F5C;&#x7528;&#x7684;&#x51DD;&#x80F6;&#x3002;&#x6B64;&#x5904;&#x63D0;&#x4F9B;&#x7684;&#x6570;&#x636E;&#x6709;&#x52A9;&#x4E8E;&#x5B9A;&#x6027;&#x751F;&#x7406;&#x6709;&#x5173;&#x7C98;&#x5F39;&#x6027;&#x7684;&#x91CD;&#x8981;&#x7684;&#x751F;&#x7269;&#x5927;&#x5206;&#x5B50;&#xFF0C;&#x53EF;&#x80FD;&#x4E5F;&#x6709;&#x52A9;&#x4E8E;&#x63ED;&#x793A;&#x590D;&#x6742;&#x5F02;&#x6784;&#x7F51;&#x7EDC;&#x73AF;&#x5883;&#x4E0B;&#x7684;&#x9AD8;&#x5206;&#x5B50;&#x51DD;&#x80F6;&#x7684;&#x5C0F;&#x7C92;&#x5B50;&#x7684;&#x6269;&#x6563;&#x8FD0;&#x52A8;&#x3002;

&#x7C98;&#x5F39;&#x6027;&#x548C;&#x732A;&#x80C3;&#x9ECF;&#x86CB;&#x767D;&#x7684;&#x52A8;&#x6001;&#x3002;

Gastric mucin is a glycoprotein known to undergo a pH-dependent sol-gel transition that is crucial to the protective function of the gastric mucus layer in mammalian stomachs. We present microscope-based dynamic light scattering data on porcine gastric mucin at pH 6 (solution) and pH 2 (gel) with and without the presence of tracer particles. The data provide a measurement of the microscale viscosity and the shear elastic modulus as well as an estimate of the mesh size of the gel formed at pH 2. We observe that the microscale viscosity in the gel is about 100-fold lower than its macroscopic viscosity, suggesting that large pores open up in the gel reducing frictional effects. The data presented here help to characterize physiologically relevant viscoelastic properties of an important biological macromolecule and may also serve to shed light on diffusive motion of small particles in the complex heterogeneous environment of a polymer gel network.

Viscoelastic properties and dynamics of porcine gastric mucin.

Mucine gastrique est une glycoprot&eacute;ine qui subissent une transition sol-gel de pH-d&eacute;pendante qui est essentielle &agrave; la fonction de protection de la couche de mucus gastrique dans l&#39;estomac des mammif&egrave;res. Nous pr&eacute;sentons des donn&eacute;es de diffusion de lumi&egrave;re dynamique ax&eacute;e sur le microscope sur la mucine gastrique porcine &agrave; pH 6 (solution) et pH 2 (gel) avec et sans la pr&eacute;sence de particules de traceur. Les donn&eacute;es fournissent une mesure de la viscosit&eacute; de la micro-&eacute;chelle et le module &eacute;lastique de cisaillement, ainsi qu&#39;une estimation de la taille des mailles du gel form&eacute; &agrave; pH 2. Nous observons que la viscosit&eacute; de la micro-&eacute;chelle dans le gel est environ 100 fois plus faible que sa viscosit&eacute; macroscopique, ce qui sugg&egrave;re que gros pores ouverts vers le haut dans le gel r&eacute;duit les frottements. Les donn&eacute;es pr&eacute;sent&eacute;es ici aident &agrave; caract&eacute;riser les propri&eacute;t&eacute;s visco&eacute;lastiques physiologiquement pertinents d&#39;une macromol&eacute;cule biologique importante et peuvent aussi servir &agrave; faire la lumi&egrave;re sur le mouvement diffusif de petites particules dans l&#39;environnement complexe et h&eacute;t&eacute;rog&egrave;ne d&#39;un r&eacute;seau de gel de polym&egrave;re.

Propri&eacute;t&eacute;s visco&eacute;lastiques et dynamique des mucines gastrique.

Viskoelastischen Eigenschaften und Dynamik von Schweine-Mucin.

Gastrica mucina &egrave; una glicoproteina conosciuta a subire una transizione sol-gel di pH-dipendente che &egrave; cruciale per la funzione protettiva dello strato di muco gastrico in stomaci dei mammiferi. Vi presentiamo i dati basati su microscopio diffusione dinamica della luce sulla suina mucina gastrica a pH 6 (soluzione) e pH 2 (gel) con e senza la presenza di particelle di tracciante. I dati forniscono una misura della viscosit&agrave; su microscala e il modulo elastico di taglio nonch&eacute; una stima le dimensioni delle maglie del gel formato a pH 2. Osserviamo che la viscosit&agrave; di Microscala nel gel &egrave; circa 100 volte inferiore alla sua viscosit&agrave; macroscopica, suggerendo che grandi pori Apri nel gel di ridurre gli effetti di attrito. I dati presentati qui aiutano a caratterizzare le propriet&agrave; viscoelastiche fisiologicamente rilevanti di un&#39;importante macromolecola biologica e possono anche servire a far luce sul movimento diffusivo di piccole particelle nell&#39;ambiente eterogeneo complesso di una rete di gel polimero.

Propriet&agrave; viscoelastiche e la dinamica della suina mucina gastrica.

&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3;&#x7CD6;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x54FA;&#x4E73;&#x985E;&#x306E;&#x80C3;&#x306E;&#x80C3;&#x7C98;&#x6DB2;&#x5C64;&#x306E;&#x4FDD;&#x8B77;&#x306E;&#x6A5F;&#x80FD;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x91CD;&#x8981; pH &#x4F9D;&#x5B58;&#x6027;&#x30BE;&#x30EB;-&#x30B2;&#x30EB;&#x8EE2;&#x79FB;&#x3092;&#x53D7;&#x3051;&#x308B;&#x3053;&#x3068;&#x304C;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3067;&#x3059;&#x3002;&#x30D6;&#x30BF;&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3; pH 6 &#x3067; (&#x30BD;&#x30EA;&#x30E5;&#x30FC;&#x30B7;&#x30E7;&#x30F3;) &#x304A;&#x3088;&#x3073; pH 2 &#xFF08;&#x30B2;&#x30EB;&#xFF09; &#x3068;&#x30C8;&#x30EC;&#x30FC;&#x30B5;&#x30FC;&#x7C92;&#x5B50;&#x306E;&#x5B58;&#x5728;&#x306A;&#x3057;&#x306B;&#x9855;&#x5FAE;&#x93E1;&#x30D9;&#x30FC;&#x30B9;&#x306E;&#x52D5;&#x7684;&#x5149;&#x6563;&#x4E71;&#x30C7;&#x30FC;&#x30BF;&#x3092;&#x63D0;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x30C7;&#x30FC;&#x30BF; &#x30DE;&#x30A4;&#x30AF;&#x30ED; &#x30B9;&#x30B1;&#x30FC;&#x30EB;&#x7C98;&#x5EA6;&#x3068;&#x305B;&#x3093;&#x65AD;&#x5F3E;&#x6027;&#x7387;&#x306E;&#x6E2C;&#x5B9A;&#x3060;&#x3051;&#x3067;&#x306A;&#x304F; pH 2 &#x3067;&#x5F62;&#x6210;&#x3055;&#x308C;&#x308B;&#x30B2;&#x30EB;&#x306E;&#x30E1;&#x30C3;&#x30B7;&#x30E5; &#x30B5;&#x30A4;&#x30BA;&#x306E;&#x898B;&#x7A4D;&#x3082;&#x308A;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x3001;&#x30DE;&#x30A4;&#x30AF;&#x30ED; &#x30B9;&#x30B1;&#x30FC;&#x30EB;&#x7C98;&#x5EA6;&#x3001;&#x30B2;&#x30EB;&#x3067;&#x305D;&#x306E;&#x5DE8;&#x8996;&#x7684;&#x7C98;&#x5EA6;&#x3088;&#x308A;&#x7D04; 100 &#x500D;&#x4F4E;&#x3044;&#x3053;&#x3068;&#x304C;&#x5927;&#x304C;&#x6469;&#x64E6;&#x306E;&#x5F71;&#x97FF;&#x3092;&#x6E1B;&#x3089;&#x3059;&#x3053;&#x3068;&#x3067;&#x30B2;&#x30EB;&#x3092;&#x958B;&#x3044;&#x3066;&#x6BDB;&#x7A74;&#x3092;&#x793A;&#x5506;&#x89B3;&#x5BDF;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x306B;&#x63D0;&#x793A;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x751F;&#x7406;&#x95A2;&#x9023;&#x91CD;&#x8981;&#x306E;&#x751F;&#x4F53;&#x9AD8;&#x5206;&#x5B50;&#x306E;&#x7C98;&#x5F3E;&#x6027;&#x7279;&#x6027;&#x3092;&#x52A9;&#x3051;&#x308B;&#x3001;&#x307E;&#x305F;&#x5FAE;&#x7C92;&#x5B50;&#x9AD8;&#x5206;&#x5B50;&#x30B2;&#x30EB; &#x30CD;&#x30C3;&#x30C8;&#x30EF;&#x30FC;&#x30AF;&#x306E;&#x8907;&#x96D1;&#x306A;&#x7570;&#x6A5F;&#x7A2E;&#x6DF7;&#x5728;&#x74B0;&#x5883;&#x3067;&#x306E;&#x62E1;&#x6563;&#x904B;&#x52D5;&#x306B;&#x5149;&#x3092;&#x5F53;&#x3066;&#x308B;&#x306E;&#x306B;&#x5F79;&#x7ACB;&#x3064;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x7C98;&#x5F3E;&#x6027;&#x7279;&#x6027;&#x3068;&#x30D6;&#x30BF;&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3;&#x306E;&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30AF;&#x30B9;&#x3002;

&#xC704; mucin &#xD3EC;&#xC720;&#xB958; &#xC704;&#xC7A5;&#xC5D0;&#xC11C; &#xC704; &#xC810;&#xC561; &#xCE35;&#xC758; &#xBCF4;&#xD638; &#xAE30;&#xB2A5;&#xC5D0; &#xC911;&#xC694; &#xD55C; pH &#xC885;&#xC18D; &#xC194;-&#xC824; &#xC804;&#xC774; &#xC218;&#xC220;&#xB85C; &#xC54C;&#xB824;&#xC9C4; &#xB2F9;&#xB2E8;&#xBC31;&#xC9C8; &#xC774;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xB3FC;&#xC9C0; &#xC704;&#xC7A5; mucin pH 6&#xC5D0;&#xC11C; (&#xC194;&#xB8E8;&#xC158;) &#xBC0F; pH 2 (&#xC824;) &#xD2B8; &#xB808;&#xC774; &#xC11C; &#xC785;&#xC790;&#xC758; &#xC874;&#xC7AC; &#xC720;&#xBB34;&#xC5D0; &#xB3D9;&#xC801; &#xAD11; &#xC0B0;&#xB780; &#xD604;&#xBBF8;&#xACBD;-&#xAE30;&#xBC18; &#xB370;&#xC774;&#xD130; &#xD604;&#xC7AC;. &#xB370;&#xC774;&#xD130; &#xC81C;&#xACF5; microscale &#xC810;&#xB3C4; &#xBC0F; &#xC804;&#xB2E8; &#xD0C4;&#xC131; &#xACC4;&#xC218; &#xCE21;&#xC815; pH 2&#xC5D0;&#xC11C; &#xD615;&#xC131; &#xB41C; &#xAC94;&#xC758; &#xBA54;&#xC26C; &#xD06C;&#xAE30;&#xB97C; &#xC608;&#xC0C1; &#xD569;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC824;&#xC5D0;&#xC11C; microscale &#xC810;&#xB3C4; &#xC57D; &#xC57D;&#xC758; &#xAC70;&#xC2DC;&#xC801;&#xC778; &#xC810;&#xB3C4; &#xBCF4;&#xB2E4; &#xB0AE;&#xC740; &#xB300;&#xD615; &#xC138;&#xACF5; &#xB9C8;&#xCC30; &#xD6A8;&#xACFC; &#xC904;&#xC774;&#xB294; &#xC824; &#xC5F4;&#xC5B4; &#xC81C;&#xC548; &#xAD00;&#xCC30;. &#xC5EC;&#xAE30;&#xC5D0; &#xC81C;&#xC2DC; &#xB41C; &#xB370;&#xC774;&#xD130;&#xB294; &#xC911;&#xC694; &#xD55C; &#xC0DD;&#xCCB4; &#xACE0;&#xBD84;&#xC790;&#xC758; &#xC21C;&#xC218; &#xAD00;&#xB828; &#xC9C0;&#xB2C8;&#xB294; &#xC18D;&#xC131;&#xC758; &#xD2B9;&#xC131;&#xC744; &#xB3C4;&#xC6C0;&#xB9D0;&#xACFC; &#xD3F4;&#xB9AC;&#xBA38; &#xC824; &#xB124;&#xD2B8;&#xC6CC;&#xD06C;&#xC758; &#xBCF5;&#xC7A1; &#xD55C; &#xC774;&#xAE30;&#xC885; &#xD658;&#xACBD;&#xC5D0;&#xC11C; &#xC791;&#xC740; &#xC785;&#xC790;&#xC758; &#xD37C;&#xC9C0;&#xB294; &#xBAA8;&#xC158;&#xC5D0; &#xD574; &#xC8FC;&#xC2E4; &#xBD09;&#xC0AC; &#xB610;&#xD55C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC9C0;&#xB2C8;&#xB294; &#xC18D;&#xC131; &#xBC0F; &#xB3FC;&#xC9C0; &#xC704; mucin&#xC758; &#xC5ED;&#xD559;&#xC785;&#xB2C8;&#xB2E4;.

Mucina g&aacute;strica es una glicoprote&iacute;na conocida para someterse a una transici&oacute;n solgel pH-dependiente que es crucial para la funci&oacute;n protectora de la capa de moco g&aacute;strico en el est&oacute;mago mam&iacute;fero. Presentamos los datos de la dispersi&oacute;n de la luz din&aacute;mica basadas en microscopio en mucina g&aacute;strica porcina a pH 6 (soluci&oacute;n) y pH 2 (gel) con y sin la presencia de part&iacute;culas de trazador. Los datos proporcionan una medici&oacute;n de la viscosidad de la microescala y el m&oacute;dulo el&aacute;stico del esquileo, as&iacute; como una estimaci&oacute;n de la malla del gel formado a pH 2. Observamos que la viscosidad de microescala en el gel es aproximadamente cien veces menor que su viscosidad macrosc&oacute;pico, sugiriendo que grandes poros abre en el gel reducir rozamientos. Los datos presentados aqu&iacute; ayudan a caracterizar las propiedades viscoel&aacute;sticas fisiol&oacute;gicamente relevantes de una macromol&eacute;cula biol&oacute;gica importante y tambi&eacute;n pueden servir para arrojar luz sobre movimiento difusivo de peque&ntilde;as part&iacute;culas en el ambiente heterog&eacute;neo y complejo de una red de gel pol&iacute;mero.

Propiedades viscoel&aacute;sticas y din&aacute;mica de la mucina g&aacute;strica porcina.

Mammalian gastric mucin, at high concentration, is known to form a gel at low pH, behavior essential to the protection of the stomach from auto-digestion. Atomic force microscopy (AFM) measurements of dilute solutions of porcine gastric mucin in an aqueous environment in the pH range 6-2 provide a direct visualization of extended fiberlike molecules at pH 6 that aggregate at pH 4 and below forming well-defined clusters at pH 2. The clusters consist of 10 or less molecules. AFM images of mucin at high concentration at pH 2 reveal clusters similar to those seen in the dilute solutions at low pH. We also imaged human gastric mucus revealing a network having a "pearl necklace" structure. The "pearls" are similar in size to the clusters found in the purified porcine gastric mucin gels. AFM images of deglycosylated mucin reveal that the deglycosylated portions of the molecule re-fold into compact, globular structures suggesting that the oligosaccharide chains are important in maintaining the extended conformation of mucin. However, the oligosaccharides do not appear to be directly involved in the aggregation at low pH, as clusters of similar size are observed at pH 2 in both native and deglycosylated mucin.

Atomic force microscopy reveals aggregation of gastric mucin at low pH.

We have used small-angle light-scattering (SALS), microscopy, and measurements to study structural changes produced in unbuffered agarose gels as ions migrate under applied electric fields (3-20 V/cm). Anisotropic, bowtielike, light-scattering patterns were observed, whose development occurred more quickly at higher fields. The horizontal lobes were more pronounced at higher polymer concentration. Analysis of the SALS data with a simple model of scattering from anisotropic rods in an electric field is consistent with anisotropic rodlike domains on the order of 10-15 microm in length, which align perpendicular to the electric field. The anisotropic domains in the gel reach almost the same level of orientation, regardless of the field strength. Microscope imaging revealed anisotropic domains on the same length scale, also aligned perpendicular to the field. Profiles of pH variation across the gel, measured by video photography, indicate that the anisotropic patterns appear when the H+ and OH- ions, migrating in opposite directions, meet. Calculations of pH profiles using a model based on electrodiffusion reproduce several features of measured pH profiles, including the power-law dependence on the electric field of the time at which the oppositely charged fronts meet. Ions migrating from both ends of the gel produce pH changes that are correlated with macroscopic shrinking and orientation of the gel.

Electrolysis induces gradients and domain orientation in agarose gels.

Time-resolved small-angle x-ray scattering measurements reveal that a long-lived intermediate bcc state forms when a poly(styrene-b-isoprene) diblock copolymer solution in an isoprene selective solvent is rapidly cooled from the disordered micellar fluid at high temperature to an equilibrium fcc state. The kinetics of the epitaxial growth of the [111] fcc peak from the [110] bcc peak was obtained by fitting the scattering data to a simple model of the transformation. The growth of the [111] fcc peak agrees with the Avrami model of nucleation and growth kinetics with an exponent n=1.4, as does the initial decay of the [110] bcc peak, with an exponent n=1.3. The data were also found to be in good agreement with the Cahn model of grain boundary nucleation and growth.

Kinetics of disorder-to-fcc phase transition via an intermediate bcc state.

Gastrica mucina, una glicoproteina ad alto peso molecolare, &egrave; responsabile di fornire le propriet&agrave; gelificanti e funzione protettiva dello strato di muco gastrico. Misurazioni reologia alla rinfusa nel regime viscoelastici lineari mostrano che quella gastrica mucina subisce una transizione sol-gel di pH-dipendente da una soluzione viscoelastica a pH neutro ad un gel viscoelastico morbido in condizioni acide, con la transizione che si verificano nei pressi di pH 4. Oltre al comportamento di gelificazione pH-dipendente in questo sistema, ulteriori studi reologici sotto deformazioni non lineari rivelano taglio diradamento e un limite di snervamento apparente in questo materiale sono anche fortemente influenzati dal pH.

Reologia della mucina gastrica esibisce una transizione sol-gel di pH-dipendente.

Magen Mucin, ein Hochmolekulares Glykoprotein, ist verantwortlich f&uuml;r die Bereitstellung der Gel bildende Eigenschaften und Schutzfunktion der Magen Schleim Schicht. Massen Rheologie Messungen im linearen viskoelastischen Regime zeigen, dass dieser Magen Mucin einen pH-Wert-abh&auml;ngige Sol-Gel-&Uuml;bergang von eine Viskoelastische L&ouml;sung bei neutralem pH-Wert zu einem weichen viskoelastischen Gel unter sauren Bedingungen, mit &Uuml;bergang stattfindet, in der N&auml;he von pH 4 unterzogen wird. Zus&auml;tzlich zu pH-Wert-abh&auml;ngige Gelbildung Verhalten in diesem System enth&uuml;llen weitere Rheologische Untersuchungen unter nichtlineare Verformungen Effilier Schere und eine scheinbare Flie&szlig;spannung in diesem Material, das auch stark vom pH-Wert beeinflusst werden.

Rheologie von Magen Mucin weist einen pH-Wert-abh&auml;ngige Sol-Gel-&Uuml;bergang.

Mucine gastrique, une glycoprot&eacute;ine de haut poids mol&eacute;culaire, est responsable de fournir les propri&eacute;t&eacute;s formatrices de gel et la fonction de protection de la couche de mucus gastrique. Les mesures de rh&eacute;ologie en vrac dans le r&eacute;gime de visco&eacute;lastique lin&eacute;aire montrent que la mucine gastrique subit une transition de d&eacute;pendante du pH sol-gel d&#39;une solution visco&eacute;lastique &agrave; pH neutre &agrave; un gel visco&eacute;lastique doux dans des conditions acides, la transition se produisant pr&egrave;s de pH 4. En plus du comportement de g&eacute;lification d&eacute;pendante du pH dans ce syst&egrave;me, plus &eacute;tudes rh&eacute;ologiques sous des d&eacute;formations non-lin&eacute;aires r&eacute;v&egrave;lent amincissement de cisaillement et une limite d&#39;&eacute;lasticit&eacute; apparente dans cette mati&egrave;re, qui sont aussi fortement influenc&eacute;e par le pH.

Rh&eacute;ologie de la mucine gastrique montre une transition sol-gel de pH-d&eacute;pendante.

&#x80C3;&#x9ECF;&#x6DB2;&#xFF0C;&#x9AD8;&#x5206;&#x5B50;&#x91CF;&#x7CD6;&#x86CB;&#x767D;&#xFF0C;&#x662F;&#x8D1F;&#x8D23;&#x63D0;&#x4F9B;&#x7684;&#x51DD;&#x80F6;&#x5316;&#x6027;&#x80FD;&#x548C;&#x80C3;&#x7C98;&#x6DB2;&#x5C42;&#x7684;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x3002;&#x5927;&#x5BB9;&#x91CF;&#x6D41;&#x53D8;&#x6D4B;&#x91CF;&#x7EBF;&#x6027;&#x7C98;&#x5F39;&#x6027;&#x5236;&#x5EA6;&#x4E2D;&#x7684;&#x663E;&#x793A;&#x8FD9;&#x80C3;&#x9ECF;&#x6DB2;&#x7ECF;&#x5386; pH &#x4F9D;&#x8D56;&#x578B;&#x6EB6;&#x80F6;-&#x51DD;&#x80F6;&#x4ECE;&#x8FC7;&#x6E21; pH &#x4E3A;&#x4E2D;&#x6027;&#x7684;&#x7C98;&#x5F39;&#x6027;&#x89E3;&#x51B3;&#x65B9;&#x6848;&#x5230;&#x8F6F;&#x7C98;&#x5F39;&#x6027;&#x51DD;&#x80F6;&#x5728;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x4E0B;&#xFF0C;ph &#x503C; 4 &#x9644;&#x8FD1;&#x53D1;&#x751F;&#x7684;&#x8FC7;&#x6E21;&#x3002;&#x5728;&#x6B64;&#x7CFB;&#x7EDF;&#x4E2D;&#x7684; pH &#x4F9D;&#x8D56;&#x578B;&#x51DD;&#x80F6;&#x884C;&#x4E3A;&#xFF0C;&#x8FDB;&#x4E00;&#x6B65;&#x4E0B;&#x975E;&#x7EBF;&#x6027;&#x53D8;&#x5F62;&#x7684;&#x6D41;&#x53D8;&#x5B66;&#x7814;&#x7A76;&#x63ED;&#x793A;&#x526A;&#x5207;&#x7A00;&#x5316;&#x548C;&#x5728;&#x8FD9;&#x79CD;&#x6750;&#x6599;&#x7684; ph &#x503C;&#x4E5F;&#x9AD8;&#x5EA6;&#x5F71;&#x54CD;&#x660E;&#x663E;&#x5C48;&#x670D;&#x5E94;&#x529B;&#x3002;

&#x80C3;&#x9ECF;&#x6DB2;&#x6D41;&#x53D8;&#x5C55;&#x54C1; pH &#x4F9D;&#x8D56;&#x578B;&#x6EB6;&#x80F6;-&#x51DD;&#x80F6;&#x8FC7;&#x6E21;&#x3002;

Gastric mucin, a high molecular weight glycoprotein, is responsible for providing the gel-forming properties and protective function of the gastric mucus layer. Bulk rheology measurements in the linear viscoelastic regime show that gastric mucin undergoes a pH-dependent sol-gel transition from a viscoelastic solution at neutral pH to a soft viscoelastic gel in acidic conditions, with the transition occurring near pH 4. In addition to pH-dependent gelation behavior in this system, further rheological studies under nonlinear deformations reveal shear thinning and an apparent yield stress in this material which are also highly influenced by pH.

Rheology of gastric mucin exhibits a pH-dependent sol-gel transition.

&#x9AD8;&#x5206;&#x5B50;&#x91CF;&#x7CD6;&#x80C3;&#x7C98;&#x6DB2;&#x30B2;&#x30EB;&#x5F62;&#x6210;&#x30D7;&#x30ED;&#x30D1;&#x30C6;&#x30A3;&#x3068;&#x80C3;&#x7C98;&#x6DB2;&#x5C64;&#x306E;&#x9632;&#x5FA1;&#x6A5F;&#x80FD;&#x3092;&#x63D0;&#x4F9B;&#x3059;&#x308B;&#x305F;&#x3081;&#x62C5;&#x5F53;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x305D;&#x306E;&#x80C3;&#x30E0;&#x30C1;&#x30F3;&#x306F; pH &#x4F9D;&#x5B58;&#x6027;&#x30BE;&#x30EB;-&#x30B2;&#x30EB;&#x79FB;&#x884C;&#x7C98;&#x5F3E;&#x6027;&#x30BD;&#x30EA;&#x30E5;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306F;&#x4E2D;&#x6027; pH &#x304B;&#x3089;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x3067;&#x67D4;&#x3089;&#x304B;&#x3044;&#x7C98;&#x5F3E;&#x6027;&#x30B2;&#x30EB;&#x306B; pH 4 &#x4ED8;&#x8FD1;&#x3067;&#x767A;&#x751F;&#x3059;&#x308B;&#x79FB;&#x884C;&#x3092;&#x53D7;&#x3051;&#x308B;&#x4E00;&#x62EC;&#x7DDA;&#x5F62;&#x7C98;&#x5F3E;&#x6027;&#x9818;&#x57DF;&#x306B;&#x304A;&#x3051;&#x308B;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x306E;&#x6E2C;&#x5B9A;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x3067;&#x306F; pH &#x4F9D;&#x5B58;&#x6027;&#x30B2;&#x30EB;&#x5316;&#x52D5;&#x4F5C;&#x306E;&#x307B;&#x304B;&#x306B;&#x3001;&#x3055;&#x3089;&#x306B;&#x305B;&#x3093;&#x65AD;&#x3092;&#x9593;&#x4F10;&#x3057;&#x3001;&#x898B;&#x304B;&#x3051;&#x306E;&#x964D;&#x4F0F;&#x5FDC;&#x529B;&#x306B;&#x3088;&#x308B; pH &#x306E;&#x5F71;&#x97FF;&#x3082;&#x975E;&#x5E38;&#x306B;&#x3053;&#x306E;&#x6750;&#x6599;&#x3067;&#x306E;&#x975E;&#x7DDA;&#x5F62;&#x5909;&#x5F62;&#x4E0B;&#x3067;&#x306E;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x306E;&#x7814;&#x7A76;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x307E;&#x3059;&#x3002;

&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3;&#x306E; pH &#x4F9D;&#x5B58;&#x6027;&#x30BE;&#x30EB;-&#x30B2;&#x30EB;&#x8EE2;&#x79FB;&#x3092;&#x5C55;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#xC704; mucin, &#xB192;&#xC740; &#xBD84;&#xC790;&#xB7C9; &#xB2F9;&#xB2E8;&#xBC31;&#xC9C8;&#xC740; &#xC824; &#xD615;&#xC131; &#xC18D;&#xC131;&#xACFC; &#xC704; &#xC810;&#xC561; &#xCE35;&#xC758; &#xBCF4;&#xD638; &#xAE30;&#xB2A5;&#xC744; &#xC81C;&#xACF5; &#xD569;&#xB2C8;&#xB2E4;. &#xC120;&#xD615; &#xC810; &#xD0C4;&#xC131; &#xC815;&#xAD8C;&#xC5D0;&#xC11C; &#xB300;&#xB7C9; &#xB808; &#xC62C;&#xB85C; &#xC9C0; &#xCE21;&#xC815; &#xADF8; &#xC704; mucin &#xACAA; &#xC2B5; pH 4 &#xADFC;&#xCC98;&#xC5D0; &#xBC1C;&#xC0DD; &#xD558;&#xB294; &#xC804;&#xD658; &#xB41C; &#xC0B0; &#xC131; &#xC870;&#xAC74;&#xC5D0;&#xC11C; &#xBD80;&#xB4DC;&#xB7EC;&#xC6B4; &#xC9C0;&#xB2C8;&#xB294; &#xC824;&#xC744; &#xC911;&#xB9BD; &#xC0B0;&#xB3C4;&#xC5D0;&#xC11C; &#xC9C0;&#xB2C8;&#xB294; &#xC194;&#xB8E8;&#xC158;&#xC5D0;&#xC11C; pH &#xC885;&#xC18D; &#xC194;-&#xC824; &#xC804;&#xD658;&#xC744; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xC774; &#xC2DC;&#xC2A4;&#xD15C;&#xC5D0;&#xC11C; pH &#xC885;&#xC18D; &#xAC94; &#xD654; &#xB3D9;&#xC791; &#xC774;&#xC678;&#xC5D0; &#xCD94;&#xAC00; &#xC720; &#xBCC0; &#xD559;&#xC801; &#xC5F0;&#xAD6C; &#xBE44;&#xC120;&#xD615; &#xBCC0;&#xD615; &#xC544;&#xB798; &#xACF5;&#xAC1C; &#xC804;&#xB2E8; &#xC231;&#xC774; &#xD558; &#xACE0;&#xB3C4; &#xB192;&#xC740; &#xC0B0;&#xB3C4; &#xC758;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xD558;&#xB294;&#xC774; &#xC790;&#xB8CC;&#xC5D0;&#xC11C; &#xBA85;&#xBC31;&#xD55C; &#xD56D;&#xBCF5; &#xC751;&#xB825;.

&#xC704; mucin&#xC758; &#xB808; &#xC62C;&#xB85C; &#xC9C0; pH &#xC885;&#xC18D; &#xC194;-&#xC824; &#xC804;&#xC774; &#xC804;&#xC2DC;.

Mucina g&aacute;strica, una glicoprote&iacute;na de alto peso molecular, es responsable de proporcionar las propiedades gelificante y la funci&oacute;n protectora de la capa de moco g&aacute;strico. Mediciones de reolog&iacute;a de masivas en el r&eacute;gimen de viscoel&aacute;stica lineal Mostrar que eso mucina g&aacute;strica sufre una transici&oacute;n de pH-dependent sol-gel de una soluci&oacute;n viscoel&aacute;stica en pH neutro a un gel viscoel&aacute;stico suave en condiciones &aacute;cidas, con la transici&oacute;n que ocurre cerca de pH 4. Adem&aacute;s de comportamiento de gelificaci&oacute;n pH-dependent en este sistema, m&aacute;s estudios reol&oacute;gicos bajo deformaciones no lineales revelan esquileo adelgazamiento y una aparente fluencia en este material, que son tambi&eacute;n altamente influenciado por el pH.

Reolog&iacute;a de mucina g&aacute;strica exhibe una transici&oacute;n solgel pH-dependent.

&#x5BFC;&#x81F4;&#x6E83;&#x75A1;&#x7684;&#x80C3;&#x75C5;&#x539F;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x662F;&#x552F;&#x4E00;&#x53CC;&#x7403;&#x83CC;&#x8FDB;&#x884C;&#x6B96;&#x6C11;&#x7EDF;&#x6CBB;&#x7684;&#x4EBA;&#x7684;&#x80C3;&#x82DB;&#x523B;&#x9178;&#x6027;&#x73AF;&#x5883;&#x3002;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x751F;&#x5B58;&#x5728;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x4E0B;&#x7684;&#x4EA7;&#x9176;&#x7684;&#x50AC;&#x5316;&#x6C34;&#x89E3;&#x5C3F;&#x7D20;&#x4EA7;&#x751F;&#x6C28;&#xFF0C;&#x4ECE;&#x800C;&#x63D0;&#x5347;&#x5176;&#x73AF;&#x5883;&#x7684; ph &#x503C;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x80FD;&#x591F;&#x901A;&#x8FC7;&#x5728;&#x80C3;&#x58C1;&#x4E0A;&#x4ECD;&#x7136;&#x5F88;&#x5DEE;&#x7684;&#x5927;&#x8863;&#x7406;&#x89E3;&#x7C98;&#x5F39;&#x6027;&#x7C98;&#x6DB2;&#x51DD;&#x80F6;&#x6E38;&#x6CF3;&#x4E2D;&#x7684;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x7684;&#x65B9;&#x5F0F;&#x3002;&#x80C3;&#x9ECF;&#x6DB2;&#x3001; &#x80C3;&#x7C98;&#x6DB2;&#x7684;&#x5173;&#x952E;&#x7C98;&#x5F39;&#x6027;&#x7EC4;&#x4EF6;&#x4EE5;&#x524D;&#x6D41;&#x53D8;&#x7814;&#x7A76;&#x8868;&#x660E;&#x8FD9;&#x79CD;&#x6750;&#x6599;&#x7684;&#x6D41;&#x53D8;&#x5B66;&#x662F;&#x4F9D;&#x8D56;&#xFF0C;pH &#x4E3A;&#x4E2D;&#x6027;&#x7684;&#x7C98;&#x7A20;&#x6EB6;&#x6DB2;&#x4ECE;&#x8FC7;&#x6E21;&#x5230;&#x4E00;&#x79CD;&#x51DD;&#x80F6;&#x4F53;&#x5728;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x4E0B; ph &#x503C;&#x3002;&#x732A;&#x80C3;&#x9ECF;&#x86CB;&#x767D; (PGM) &#x6563;&#x88C5;&#x6D41;&#x53D8;&#x6D4B;&#x91CF;&#x663E;&#x793A; ph &#x503C;&#x9AD8;&#x7A0B;&#x7684;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x8BF1;&#x5BFC;&#x7C98;&#x5F39;&#x6027;&#x6A21;&#x91CF;&#x6025;&#x5267;&#x51CF;&#x5C11;&#x3002;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x5728;&#x80C3;&#x9ECF;&#x86CB;&#x767D;&#x5728;&#x9178;&#x6027;&#x548C;&#x4E2D;&#x6027;&#x7684; ph &#x503C;&#x5728;&#x6CA1;&#x6709;&#x5C3F;&#x7D20;&#x7684;&#x52A8;&#x529B;&#x7684;&#x663E;&#x5FAE;&#x955C;&#x7814;&#x7A76;&#x8868;&#x660E;&#x7EC6;&#x83CC;&#x5728;&#x9AD8; ph &#x503C;&#xFF0C;&#x81EA;&#x7531;&#x6E38;&#x6CF3;&#x548C;&#x5F3A;&#x70C8;&#x88AB;&#x9650;&#x5236;&#x5728;&#x4F4E; ph &#x503C;&#x3002;&#x901A;&#x8FC7;&#x4F7F;&#x7528;&#x53CC;&#x5149;&#x5B50;&#x8367;&#x5149;&#x663E;&#x5FAE;&#x955C;&#x56FE;&#x50CF;&#x4E0E;&#x5C3F;&#x7D20;&#x76EE;&#x524D;&#x6211;&#x4EEC;&#x663E;&#x793A;&#x5E73;&#x79FB;&#x52A8;&#x529B;&#x7531;&#x7EC6;&#x83CC;&#x7684;&#x589E;&#x76CA;&#x76F4;&#x63A5;&#x76F8;&#x5173;&#x8868;&#x793A;&#x7531; 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) &#x7684; ph &#x503C;&#x4E0A;&#x5347;&#x6700;&#x521D;&#x4F4E; pH &#x9ECF;&#x86CB;&#x767D;&#x51DD;&#x80F6;&#x4E2D;&#x7EC6;&#x83CC;&#x7684;&#x52A8;&#x529B;&#xFF0C;ph &#x503C;&#x654F;&#x611F;&#x8367;&#x5149;&#x67D3;&#x6599;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x8868;&#x660E;&#x5F62;&#x87BA;&#x65CB;&#x5E7D;&#x95E8;&#x4E0D;&#x627F;&#x62C5;&#x5176;&#x901A;&#x8FC7;&#x8C61;&#x8F6F;&#x6728;&#x66FE;&#x5EFA;&#x8BAE;&#x7684;&#x90A3;&#x6837;&#xFF0C;&#x4F46;&#x800C;&#x662F;&#x901A;&#x8FC7;&#x6539;&#x53D8;&#x5176;&#x73AF;&#x5883;&#x7684;&#x6D41;&#x53D8;&#x5C5E;&#x6027;&#x5B9E;&#x73B0;&#x52A8;&#x529B;&#x901A;&#x8FC7;&#x87BA;&#x4E1D;&#x4E00;&#x6837;&#x7684;&#x7C98;&#x6DB2;&#x51DD;&#x80F6;&#x7684;&#x65B9;&#x5F0F;&#x3002;

&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x5728;&#x7C98;&#x6DB2;&#x79FB;&#x52A8;&#x901A;&#x8FC7;&#x51CF;&#x5C11;&#x9ECF;&#x86CB;&#x767D;&#x7C98;&#x5F39;&#x6027;&#x3002;

The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner in which H. pylori is able to swim through the viscoelastic mucus gel that coats the stomach wall remains poorly understood. Previous rheology studies on gastric mucin, the key viscoelastic component of gastric mucus, indicate that the rheology of this material is pH dependent, transitioning from a viscous solution at neutral pH to a gel in acidic conditions. Bulk rheology measurements on porcine gastric mucin (PGM) show that pH elevation by H. pylori induces a dramatic decrease in viscoelastic moduli. Microscopy studies of the motility of H. pylori in gastric mucin at acidic and neutral pH in the absence of urea show that the bacteria swim freely at high pH, and are strongly constrained at low pH. By using two-photon fluorescence microscopy to image the bacterial motility in an initially low pH mucin gel with urea present we show that the gain of translational motility by bacteria is directly correlated with a rise in pH indicated by 2',7'-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), a pH sensitive fluorescent dye. This study indicates that the helicoidal-shaped H. pylori does not bore its way through the mucus gel like a screw through a cork as has previously been suggested, but instead achieves motility by altering the rheological properties of its environment.

Helicobacter pylori moves through mucus by reducing mucin viscoelasticity.

Pathog&egrave;ne causant l&#39;ulc&egrave;re gastrique Helicobacter pylori est la seule bact&eacute;rie connue pour coloniser le rude milieu acide de l&#39;estomac humain. Helicobacter pylori survit dans des conditions acides en produisant de l&#39;ur&eacute;ase, enzyme qui catalyse l&#39;hydrolyse de l&#39;ur&eacute;e pour produire l&#39;ammoniaque donc &eacute;lever le pH de son environnement. Cependant, la mani&egrave;re dans laquelle H. pylori est capable de nager &agrave; travers le gel visco&eacute;lastique de mucus qui les couches de que la paroi de l&#39;estomac reste mal comprises. &Eacute;tudes ant&eacute;rieures rh&eacute;ologie mucine gastrique, la composante cl&eacute; visco&eacute;lastique de mucus gastrique, indiquent que la rh&eacute;ologie de ce mat&eacute;riau est pH d&eacute;pendant, la transition d&#39;une solution visqueuse &agrave; pH neutre &agrave; un gel dans des conditions acides. Les mesures de rh&eacute;ologie en vrac sur mucines gastrique (PGM) montrent que l&#39;&eacute;l&eacute;vation du pH par H. pylori induit une diminution dramatique de modules visco&eacute;lastiques. Des &eacute;tudes de microscopie de la motilit&eacute; de H. pylori dans la mucine gastrique &agrave; des pH acide et neutre en l&#39;absence d&#39;ur&eacute;e montrent que la bact&eacute;rie nage librement &agrave; un pH &eacute;lev&eacute; et est fortement contraint &agrave; faible pH. En utilisant la microscopie de fluorescence biphotonique &agrave; l&#39;image de la motilit&eacute; bact&eacute;rienne dans un gel de mucine initialement faible pH avec de l&#39;ur&eacute;e pr&eacute;sente, nous montrons que le gain de la motilit&eacute; translationnelle par des bact&eacute;ries est directement corr&eacute;l&eacute; avec une augmentation de pH indiqu&eacute; par 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), un fluorescent sensible de pH teindre. Cette &eacute;tude indique que la forme h&eacute;lico&iuml;dale de H. pylori ne pas ennuyer son chemin &agrave; travers le gel de mucus comme une vis dans un bouchon de Li&egrave;ge comme a &eacute;t&eacute; sugg&eacute;r&eacute; pr&eacute;c&eacute;demment, mais au contraire r&eacute;alise la motilit&eacute; en alt&eacute;rant les propri&eacute;t&eacute;s rh&eacute;ologiques de son environnement.

Helicobacter pylori parcourt les mucus en r&eacute;duisant la visco&eacute;lasticit&eacute; de mucine.

Das Geschw&uuml;r verursacht Magen-Erreger Helicobacter Pylori ist das einzige Bakterium bekannt, dass das harte saure Milieu im menschlichen Magen besiedeln. H. Pylori &uuml;berlebt in sauren Bedingungen durch die Herstellung von Urease, die Harnstoff zu Ammoniak erh&ouml;hen somit den pH-Wert ihrer Umgebung f&uuml;hren katalysiert. Die Weise, in welcher H. Pylori ist jedoch in der Lage, durch das Viskoelastische Schleim Gel zu schwimmen, die M&auml;ntel, die die Magen Wand schlecht bleibt verstanden. Fr&uuml;heren Rheologie Studien &uuml;ber Magen Mucine, die wichtigsten Viskoelastische Komponente des gastrischen Schleims, zeigen, dass die Rheologie dieses Materials pH-Wert abh&auml;ngige, &Uuml;bergang von eine z&auml;hfl&uuml;ssige L&ouml;sung bei neutralem pH-Wert ein Gel in sauren Bedingungen. Massen Rheologie Messungen an Schweinen Magen Mucin (PGM) zeigen, dass die pH-Wert-Erh&ouml;hung von H. Pylori einen dramatischen R&uuml;ckgang der Viskoelastische Modulraum induziert. Mikroskopie Studien &uuml;ber die Motilit&auml;t des H. Pylori im Magen Mucin bei Saurer und neutraler pH-Wert in Ermangelung von Harnstoff zeigen, dass die Bakterien frei an hohen pH-Wert Schwimmen und werden bei niedrigem pH-Wert stark eingeschr&auml;nkt. Mit zwei-Photonen-Mikroskopie Bild die bakterielle Motilit&auml;t in einem urspr&uuml;nglich niedrigen pH Mucin Gel mit Harnstoff vorhanden, wir zeigen, dass die Verst&auml;rkung der translatorischen Motilit&auml;t durch Bakterien direkt, mit einem pH-Wert von 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) angegeben korreliert sind, eine sensible pH-Wert-Leuchtstoff f&auml;rben. Diese Studie zeigt, dass die helicoidal-f&ouml;rmigen H. Pylori seinen Weg durch das Schleim-Gel wie eine Schraube durch einen Korken wie zuvor vorgeschlagen worden, aber stattdessen Motilit&auml;t erreicht, durch die Ver&auml;nderung der rheologischen Eigenschaftendes von seiner Umgebung nicht langweilen.

Helicobacter Pylori bewegt sich durch Schleim durch Reduzierung Mucin Viskoelastizit&auml;t.

Il patogeno che causano ulcera gastrico Helicobacter pylori &egrave; il solo batterio conosciuto a colonizzare il duro ambiente acido dello stomaco umano. H. pylori sopravvive in condizioni acide di produrre ureasi, che catalizza l&#39;idrolisi dell&#39;urea per produrre ammoniaca cos&igrave; elevando il pH del suo ambiente. Tuttavia, il modo in cui H. pylori &egrave; in grado di nuotare attraverso il gel di muco viscoelastico che cappotti che la parete dello stomaco rimane scarsamente compreso. Precedenti studi reologici su gastrico mucina, il componente chiave viscoelastico di muco gastrico, indicano che la reologia di questo materiale &egrave; pH dipendente, passando da una soluzione viscosa a pH neutro ad un gel in condizioni acide. Bulk reologia misurazioni sulla suina gastrica mucina (PGM) mostrano che elevazione del pH da H. pylori induce una diminuzione drammatica in viscoelastico moduli. Studi di microscopia di motilit&agrave; di H. pylori in mucina gastrica a pH acido e neutro in assenza di urea mostrano che i batteri nuotano liberamente a pH elevato e sono fortemente vincolati a basso pH. Utilizzando la microscopia di fluorescenza del due-fotone all&#39;immagine la motilit&agrave; batterica in un gel di mucina inizialmente basso pH con urea presente ci mostrano che il guadagno di motilit&agrave; traslazionale di batteri &egrave; direttamente correlato con un aumento del pH indicato da 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), tintura un fluorescente sensibile di pH. Questo studio indica che l&#39;h. pylori a forma elicoidale non portava la strada attraverso il gel di muco come una vite attraverso un tappo di sughero come &egrave; stato suggerito in precedenza, ma invece raggiunge la motilit&agrave; alterando le propriet&agrave; reologiche del suo ambiente.

Helicobacter pylori si muove attraverso il muco riducendo la viscoelasticit&agrave; mucina.

&#x6F70;&#x760D;&#x3092;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3059;&#x80C3;&#x75C5;&#x539F;&#x4F53;&#x30D8;&#x30EA;&#x30B3;&#x30D0;&#x30AF;&#x30BF;&#x30FC; &#x30FB; &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x306F;&#x3001;&#x30D2;&#x30C8;&#x306E;&#x80C3;&#x306E;&#x904E;&#x9177;&#x306A;&#x9178;&#x6027;&#x306E;&#x74B0;&#x5883;&#x3092;&#x690D;&#x6C11;&#x5730;&#x306B;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x552F;&#x4E00;&#x306E;&#x7D30;&#x83CC;&#x3002;H. &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x306F;&#x3001;&#x3057;&#x305F;&#x304C;&#x3063;&#x3066;&#x305D;&#x306E;&#x74B0;&#x5883;&#x306E; pH &#x3092;&#x6607;&#x964D;&#x30A2;&#x30F3;&#x30E2;&#x30CB;&#x30A2;&#x53CE;&#x91CF;&#x5C3F;&#x7D20;&#x306E;&#x52A0;&#x6C34;&#x5206;&#x89E3;&#x3092;&#x89E6;&#x5A92;&#x3059;&#x308B;&#x30A6;&#x30EC;&#x30A2;&#x30FC;&#x30BC;&#x3092;&#x751F;&#x7523;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x3067;&#x3092;&#x751F;&#x304D;&#x6B8B;&#x3063;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x65B9;&#x6CD5;&#x306F; h. &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x3067;&#x306F;&#x80C3;&#x306E;&#x58C1;&#x306E;&#x4E0D;&#x5341;&#x5206;&#x306A;&#x307E;&#x307E;&#x306E;&#x30B3;&#x30FC;&#x30C8;&#x3092;&#x7406;&#x89E3;&#x7C98;&#x5F3E;&#x6027;&#x7C98;&#x6DB2;&#x30B2;&#x30EB;&#x3092;&#x901A;&#x3057;&#x3066;&#x6CF3;&#x3050;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x80C3;&#x7C98;&#x6DB2;&#x3001;&#x80C3;&#x306E;&#x7C98;&#x6DB2;&#x306E;&#x30AD;&#x30FC;&#x7C98;&#x5F3E;&#x6027;&#x30B3;&#x30F3;&#x30DD;&#x30FC;&#x30CD;&#x30F3;&#x30C8;&#x306B;&#x95A2;&#x3059;&#x308B;&#x4EE5;&#x524D;&#x306E;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x7814;&#x7A76;&#x306F;&#x3001;&#x3053;&#x306E;&#x6750;&#x6599;&#x306E;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC; pH &#x4F9D;&#x5B58;&#x6027;&#x9178;&#x6027;&#x6761;&#x4EF6;&#x3067;&#x30B2;&#x30EB;&#x306B;&#x4E2D;&#x6027; pH &#x3067;&#x7C98;&#x6027;&#x30BD;&#x30EA;&#x30E5;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x304B;&#x3089;&#x79FB;&#x884C;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x30D6;&#x30BF;&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3; (PGM) &#x306E;&#x4E00;&#x62EC;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x6E2C;&#x5B9A;&#x306F; pH &#x6A19;&#x9AD8;&#x30D4;&#x30ED;&#x30EA;&#x306B;&#x3088;&#x308B;&#x7C98;&#x5F3E;&#x6027;&#x4FC2;&#x6570;&#x306E;&#x5287;&#x7684;&#x306A;&#x6E1B;&#x5C11;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x9855;&#x5FAE;&#x93E1;&#x306E;&#x7814;&#x7A76;&#x80C3;&#x6DB2;&#x30E0;&#x30C1;&#x30F3;&#x9178;&#x6027;&#x304A;&#x3088;&#x3073;&#x4E2D;&#x6027; pH &#x306B;&#x304A;&#x3051;&#x308B;&#x5C3F;&#x7D20;&#x306E;&#x4E0D;&#x5728;&#x3067;&#x306E;&#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x306E;&#x904B;&#x52D5;&#x306F;&#x7D30;&#x83CC;&#x304C;&#x9AD8;&#x3044; pH &#x3067;&#x81EA;&#x7531;&#x306B;&#x6CF3;&#x3050;&#x3057;&#x3001;&#x4F4E;&#x3044; pH &#x3067;&#x5F37;&#x304F;&#x5236;&#x7D04;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;. &#x3057;&#x307E;&#x3059;&#x3002;2 &#x5149;&#x5B50;&#x86CD;&#x5149;&#x9855;&#x5FAE;&#x93E1;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x3001;&#x5F53;&#x521D;&#x4F4E; pH &#x7C98;&#x6DB2;&#x30B2;&#x30EB;&#x306E;&#x6211;&#x3005; &#x306E;&#x4E26;&#x9032;&#x904B;&#x52D5;&#x6027;&#x7D30;&#x83CC;&#x306B;&#x3088;&#x308B;&#x5229;&#x5F97;&#x306E;&#x76F4;&#x63A5; 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein &#xFF08;BCECF) &#x306B;&#x3088;&#x3063;&#x3066;&#x793A;&#x3055;&#x308C;&#x305F; pH &#x306E;&#x4E0A;&#x6607;&#x3068;&#x76F8;&#x95A2;&#x3092;&#x793A;&#x3059;&#x5C3F;&#x7D20;&#x5B58;&#x5728;&#x306E;&#x7D30;&#x83CC;&#x904B;&#x52D5;&#x30A4;&#x30E1;&#x30FC;&#x30B8;&#x306B; pH &#x306E;&#x654F;&#x611F;&#x306A;&#x86CD;&#x5149;&#x67D3;&#x6599;&#x3057;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x306F;&#x87BA;&#x65CB;&#x5F62;&#x30D4;&#x30ED;&#x30EA;&#x7C98;&#x6DB2;&#x30B2;&#x30EB;&#x3092;&#x901A;&#x3057;&#x3066;&#x4EE5;&#x524D;&#x63D0;&#x6848;&#x3055;&#x308C;&#x3066;&#x304D;&#x305F;&#x304C;&#x3001;&#x4EE3;&#x308F;&#x308A;&#x306B;&#x305D;&#x306E;&#x74B0;&#x5883;&#x306E;&#x30EC;&#x30AA;&#x30ED;&#x30B8;&#x30FC;&#x7279;&#x6027;&#x3092;&#x5909;&#x66F4;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x308A;&#x3001;&#x904B;&#x52D5;&#x6027;&#x3092;&#x5B9F;&#x73FE;&#x3001;&#x30B3;&#x30EB;&#x30AF; &#x30B9;&#x30AF;&#x30EA;&#x30E5;&#x30FC;&#x306E;&#x3088;&#x3046;&#x306A;&#x3082;&#x306E;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x3001;&#x305D;&#x306E;&#x65B9;&#x6CD5;&#x306A;&#x3044;&#x9000;&#x5C48;&#x3057;&#x306A;&#x3044;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;

&#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x30E0;&#x30C1;&#x30F3;&#x7C98;&#x5F3E;&#x6027;&#x3092;&#x6E1B;&#x3089;&#x3059;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;&#x3092;&#x901A;&#x3057;&#x3066;&#x7C98;&#x6DB2;&#x3092;&#x79FB;&#x52D5;&#x3057;&#x307E;&#x3059;&#x3002;

&#xADA4; &#xC591;-&#xC77C;&#xC73C;&#xD0A4;&#xB294; &#xC704; &#xBCD1;&#xC6D0; &#xCCB4; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC77C;&#xB85C;&#xB9AC; &#xC2DD;&#xBBFC;&#xC9C0; &#xC778;&#xAC04;&#xC758; &#xC704;&#xC7A5;&#xC758; &#xAC70;&#xCE5C; &#xC0B0; &#xC131; &#xD658;&#xACBD;&#xC5D0; &#xC54C;&#xB824;&#xC9C4; &#xC720;&#xC77C;&#xD55C; &#xC138;&#xADE0; &#xC774;&#xB2E4;. &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC774; &#xD56D;&#xBCF5; &#xD569;&#xB2C8;&#xB2E4; &#xB530;&#xB77C;&#xC11C; &#xADF8; &#xD658;&#xACBD;&#xC758; Ph&#xB97C; &#xC62C;&#xB9AC;&#xB294; &#xC554;&#xBAA8;&#xB2C8;&#xC544; &#xC6B0; &#xB808; &#xC544;&#xC758;&#xAC00; &#xC218; &#xBD84;&#xD574; catalyzes urease &#xC0DD;&#xC0B0; &#xD558; &#xC5EC; &#xC0B0; &#xC131; &#xC870;&#xAC74;&#xC5D0;&#xC11C; &#xC0B4;&#xC544; &#xB09C;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC774; &#xC5B4;&#xB5A4; &#xBC29;&#xC2DD;&#xC73C;&#xB85C; &#xC9C0;&#xB2C8;&#xB294; &#xC810;&#xC561; &#xC824; &#xCF54;&#xD2B8; &#xC704; &#xBCBD; &#xB0A8;&#xC544; &#xC81C;&#xB300;&#xB85C; &#xC774;&#xD574;&#xC744; &#xD1B5;&#xD574; &#xC218;&#xC601;&#xC744; &#xC218; &#xC788;&#xB2E4;. &#xC704; mucin, &#xC704; &#xC810;&#xC561;&#xC758; &#xC810; &#xD0C4;&#xC131; &#xD0A4; &#xAD6C;&#xC131; &#xC694;&#xC18C;&#xC5D0; &#xB300; &#xD55C; &#xC774;&#xC804; &#xB808; &#xC62C;&#xB85C; &#xC9C0; &#xC5F0;&#xAD6C;&#xC774; &#xC790;&#xB8CC;&#xC758; &#xB808; &#xC62C;&#xB85C; &#xC9C0; pH &#xC758;&#xC874;, &#xC911;&#xC131; Ph&#xC5D0;&#xC11C; &#xC810;&#xC131; &#xC6A9;&#xC561;&#xC5D0;&#xC11C; &#xC0B0; &#xC131; &#xC870;&#xAC74;&#xC5D0;&#xC11C; &#xC824;&#xC73C;&#xB85C; &#xC804;&#xD658; &#xB418;&#xC5C8;&#xC74C;&#xC744; &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4;. &#xB3FC;&#xC9C0; &#xC704; mucin (PGM)&#xC758; &#xB300;&#xB7C9; &#xB808; &#xC62C;&#xB85C; &#xC9C0; &#xCE21;&#xC815; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130;&#xC5D0; &#xC758;&#xD574; pH &#xC0C1;&#xC2B9; &#xC720;&#xB3C4; &#xC9C0;&#xB2C8;&#xB294; &#xC751;&#xC6A9;&#xC5D0; &#xC788;&#xB294; &#xADF9;&#xC801;&#xC778; &#xAC10;&#xC18C;&#xB97C; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xC6B0; &#xB808; &#xC544;&#xC758; &#xBD80;&#xC7AC;&#xC5D0; &#xC788;&#xB294; &#xC0B0; &#xC131; &#xBC0F; &#xC911;&#xC131; Ph&#xC5D0;&#xC11C; &#xC704; mucin &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130;&#xC758; &#xC6B4;&#xB3D9; &#xC131; &#xD604;&#xBBF8;&#xACBD; &#xC5F0;&#xAD6C;&#xB294; &#xBC15;&#xD14C;&#xB9AC;&#xC544; &#xB192;&#xC740; Ph&#xC5D0;&#xC11C; &#xC790;&#xC720;&#xB86D;&#xAC8C; &#xC218;&#xC601; &#xB0AE;&#xC740; Ph&#xC5D0;&#xC11C;&#xC758; &#xC81C;&#xC57D;&#xC744; &#xAC15;&#xD558;&#xAC8C; &#xBCF4;&#xC5EC;&#xC90D;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xBC15;&#xD14C;&#xB9AC;&#xC544;&#xC5D0; &#xC758;&#xD574; &#xBCC0;&#xD658; &#xC6B4;&#xB3D9; &#xC131; &#xC99D;&#xAC00; 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF)&#xC5D0; &#xD45C;&#xC2DC; &#xB41C; ph&#xC5D0;&#xC11C; &#xC99D;&#xAC00;&#xC640; &#xC9C1;&#xC811; &#xC0C1;&#xAD00; &#xBCF4;&#xC5EC; &#xD604;&#xC7AC; &#xC6B0; &#xB808; &#xC544;&#xC640; &#xD568;&#xAED8; &#xCC98;&#xC74C; &#xB0AE;&#xC740; pH mucin &#xC824;&#xC5D0;&#xC11C; &#xC138;&#xADE0;&#xC758; &#xC6B4;&#xB3D9; &#xC131; &#xC774;&#xBBF8;&#xC9C0;&#xB97C; 2-&#xAD11;&#xC790; &#xD615;&#xAD11; &#xD604;&#xBBF8;&#xACBD; &#xAC80;&#xC0AC; &#xBC95;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; pH &#xBBFC;&#xAC10;&#xD55C; &#xD615;&#xAD11; &#xC5FC;&#xB8CC;. &#xC774; &#xC5F0;&#xAD6C;&#xB294; helicoidal &#xBAA8;&#xC591;&#xC758; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xADF8; &#xAE38;&#xC744; &#xD1B5;&#xD574; &#xC774;&#xC804;&#xC5D0; &#xC81C;&#xC548; &#xD558;&#xC9C0;&#xB9CC; &#xADF8; &#xD658;&#xACBD;&#xC758; &#xC720; &#xBCC0; &#xD559;&#xC801; &#xD2B9;&#xC131;&#xC744; &#xBCC0;&#xACBD; &#xD558; &#xC5EC; &#xC6B4;&#xB3D9; &#xC131;&#xC744; &#xC2E4;&#xD604; &#xD558;&#xB294; &#xB300;&#xC2E0; &#xCF54;&#xB974;&#xD06C; &#xC2A4;&#xD06C;&#xB958; &#xCC98;&#xB7FC; &#xC810;&#xC561; &#xC824;&#xC744; &#xB0B3;&#xC740; &#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4; &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4;.

&#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC77C;&#xB85C;&#xB9AC;&#xB294; mucin viscoelasticity&#xB97C; &#xC904;&#xC5EC; &#xC810;&#xC561;&#xC744; &#xD1B5;&#xD574; &#xC774;&#xB3D9; &#xD569;&#xB2C8;&#xB2E4;.

El pat&oacute;geno que causa &uacute;lcera g&aacute;strico Helicobacter pylori es la &uacute;nica bacteria conocida para colonizar el &aacute;spero ambiente &aacute;cido del est&oacute;mago humano. H. pylori sobrevive en condiciones &aacute;cidas por producir ureasa, que cataliza la hidr&oacute;lisis de la urea para producir amoniaco as&iacute; elevar el pH de su entorno. Sin embargo, la manera en que H. pylori es capaz de nadar a trav&eacute;s del gel moco de viscoel&aacute;stico que capas de que la pared del est&oacute;mago sigue siendo mal entendidos. Estudios previos de la reolog&iacute;a en mucina g&aacute;strica, el componente clave viscoel&aacute;stico de moco g&aacute;strico, indican que la reolog&iacute;a de este material es pH dependiente, la transici&oacute;n de una soluci&oacute;n viscosa a pH neutro a un gel en condiciones &aacute;cidas. Mediciones de reolog&iacute;a de masivas en mucina g&aacute;strica porcina (PGM) muestran que la elevaci&oacute;n del pH por H. pylori induce una disminuci&oacute;n dram&aacute;tica en m&oacute;dulos de viscoel&aacute;stica. Estudios de la microscopia de la motilidad de H. pylori en mucina g&aacute;strica a pH &aacute;cido y neutro en la ausencia de urea demuestran que las bacterias nadan libremente a un pH alto y est&aacute;n fuertemente limitadas en pH bajo. Utilizando microscop&iacute;a de fluorescencia de dos fotones a la imagen de la motilidad bacteriana en un gel de mucina inicialmente bajo pH con urea presente nos muestran que el aumento de la motilidad traslacional por bacterias se relaciona directamente con un aumento en el pH indicado por 2&#39;,7&#39;-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), un fluorescente sensible de pH del tinte. Este estudio indica que el H. pylori en forma helicoidal no llevaba su paso por el gel moco como un tornillo a trav&eacute;s de un corcho como ha sugerido anteriormente, pero en cambio logra motilidad mediante la alteraci&oacute;n de las propiedades reol&oacute;gicas de su entorno.

Helicobacter pylori se mueve a trav&eacute;s de moco mediante la reducci&oacute;n de la viscoelasticidad de mucina.

The kinetics of the transformation from the hexagonal packed cylinder (hex) phase to the face-centered-cubic (fcc) phase was simulated using Brownian dynamics for an ABA triblock copolymer in a selective solvent for the A block. The kinetics was obtained by instantaneously changing either the temperature of the system or the well-depth of the Lennard-Jones potential. Detailed analysis showed that the transformation occurred via a rippling mechanism. The simulation results indicated that the order-order transformation was a nucleation and growth process when the temperature of the system instantly jumped from 0.8 to 0.5. The time evolution of the structure factor obtained by Fourier transformation showed that the peak intensities of the hex and fcc phases could be fit well by an Avrami equation.

Kinetics of hexagonal cylinders to face-centered cubic spheres transition of triblock copolymer in selective solvent: Brownian dynamics simulation.

The bacterium Helicobacter pylori (H. pylori), has evolved to survive in the highly acidic environment of the stomach and colonize on the epithelial surface of the gastric mucosa. Its pathogenic effects are well known to cause gastritis, peptic ulcers, and gastric cancer. In order to infect the stomach and establish colonies on the mucus epithelial surface, the bacterium has to move across the gel-like gastric mucus lining of the stomach under acidic conditions. In this review we address the question of how the bacterium gets past the protective mucus barrier from a biophysical perspective. We begin by reviewing the molecular structure of gastric mucin and discuss the current state of understanding concerning mucin polymerization and low pH induced gelation. We then focus on the viscoelasticity of mucin in view of its relevance to the transport of particles and bacteria across mucus, the key first step in H. pylori infection. The second part of the review focuses on the motility of H. pylori in mucin solutions and gels, and how infection with H. pylori in turn impacts the viscoelastic properties of mucin. We present recent microscopic results tracking the motion of H. pylori in mucin solutions and gels. We then discuss how the biochemical strategy of urea hydrolysis required for survival in the acid is also relevant to the mechanism that enables flagella-driven swimming across the mucus gel layer. Other aspects of the influence of H. pylori infection such as, altering gastric mucin expression, its rate of production and its composition, and the influence of mucin on factors controlling H. pylori virulence and proliferation are briefly discussed with references to relevant literature.

The Influence of Mucus Microstructure and Rheology in Helicobacter pylori Infection.

Mucin glycoproteins consist of tandem-repeating glycosylated regions flanked by non-repetitive protein domains with little glycosylation. These non-repetitive domains are involved in polymerization of mucin and play an important role in the pH-dependent gelation of gastric mucin, which is essential for protecting the stomach from autodigestion. We examine folding of the non-repetitive sequence of PGM-2X (242 amino acids) and the von Willebrand factor vWF-C1 domain (67 amino acids) at neutral and low pH using discrete molecular dynamics (DMD) in an implicit solvent combined with a four-bead peptide model. Using the same implicit solvent parameters, folding of both domains is simulated at neutral and low pH. In contrast to vWF-C1, PGM-2X folding is strongly affected by pH as indicated by changes in the contact order, radius of gyration, free-energy landscape, and the secondary structure. Whereas the free-energy landscape of vWF-C1 shows a single minimum at both neutral and low pH, the free-energy landscape of PGM-2X is characterized by multiple minima that are more numerous and shallower at low pH. Detailed structural analysis shows that PGM-2X partially unfolds at low pH. This partial unfolding is facilitated by the C-terminal region GLU236-PRO242, which loses contact with the rest of the domain due to effective "mean-field" repulsion among highly positively charged N- and C-terminal regions. Consequently, at low pH, hydrophobic amino acids are more exposed to the solvent. In vWF-C1, low pH induces some structural changes, including an increased exposure of CYS at position 67, but these changes are small compared to those found in PGM-2X. For PGM-2X, the DMD-derived average β-strand propensity increases from 0.26 ± 0.01 at neutral pH to 0.38 ± 0.01 at low pH. For vWF-C1, the DMD-derived average β-strand propensity is 0.32 ± 0.02 at neutral pH and 0.35 ± 0.02 at low pH. The DMD-derived structural information provides insight into pH-induced changes in the folding of two distinct mucin domains and suggests plausible mechanisms of the aggregation/gelation of mucin.

Folding of pig gastric mucin non-glycosylated domains: a discrete molecular dynamics study.

The helical shape of the human stomach pathogen Helicobacter pylori has been suggested to provide mechanical advantage for penetrating the viscous stomach mucus layer. Using single-cell tracking and quantitative morphology analysis, we document marked variation in cell body helical parameters and flagellum number among H. pylori strains leading to distinct and broad speed distributions in broth and viscous gastric mucin media. These distributions reflect both temporal variation in swimming speed and morphologic variation within the population. Isogenic mutants with straight-rod morphology showed 7-21% reduction in speed and a lower fraction of motile bacteria. Mutational perturbation of flagellum number revealed a 19% increase in speed with 4 versus 3 median flagellum number. Resistive force theory modeling incorporating variation of both cell shape and flagellum number predicts qualitative speed differences of 10-30% among strains. However, quantitative comparisons suggest resistive force theory underestimates the influence of cell body shape on speed for helical shaped bacteria.

Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments.

It has frequently been hypothesized that the helical body shapes of flagellated bacteria may yield some advantage in swimming ability. In particular, the helical-shaped pathogen  is often claimed to swim like a corkscrew through its harsh gastric habitat, but there has been no direct confirmation or quantification of such claims. Using fast time-resolution and high-magnification two-dimensional (2D) phase-contrast microscopy to simultaneously image and track individual bacteria in bacterial broth as well as mucin solutions, we show that both helical and rod-shaped  rotated as they swam, producing a helical trajectory. Cell shape analysis enabled us to determine shape as well as the rotational and translational speed for both forward and reverse motions, thereby inferring flagellar kinematics. Using the method of regularized Stokeslets, we directly compare observed speeds and trajectories to numerical calculations for both helical and rod-shaped bacteria in mucin and broth to validate the numerical model. Although experimental observations are limited to select cases, the model allows quantification of the effects of body helicity, length, and diameter. We find that due to relatively slow body rotation rates, the helical shape makes at most a 15% contribution to propulsive thrust. The effect of body shape on swimming speeds is instead dominated by variations in translational drag required to move the cell body. Because helical cells are one of the strongest candidates for propulsion arising from the cell body, our results imply that quite generally, swimming speeds of flagellated bacteria can only be increased a little by body propulsion.

Helical and rod-shaped bacteria swim in helical trajectories with little additional propulsion from helical shape.

In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.

The biology of mucus: Composition, synthesis and organization.

We present particle tracking microrheology results on human mucins, isolated from normal surface and gland mucosa and one tumor sample, and examine the motility of Helicobacter pylori in these mucins. At 1.5% concentration human mucin solutions are purely viscous, with viscosity η (gland mucin) > η (surface mucin) > η (tumor mucin). In the presence of motile H. pylori bacteria, particle diffusion is enhanced, with diffusivity D(tumor mucin) > D(gland mucin) > D(surface mucin). The surface and tumor mucin solutions exhibit an elastic response in the presence of bacteria. Taken together these results imply that particle diffusion and active swimming are coupled and impact the rheology of mucin solutions. Both J99 wild type (WT) and its isogenic ΔbabA/ΔsabA mutant swam well in broth or PGM solutions. However, the human mucins affected their motility differently, rendering them immotile in certain instances. The distribution of swimming speeds in human mucin solutions was broader with a large fraction of fast swimmers compared to PGM and broth. The bacteria swam fastest in the tumor mucin solution correlating with it having the lowest viscosity of all mucin solutions. Overall, these results suggest that mucins from different tissue locations and disease status differ in their microrheological properties and their effect on H. pylori motility.

Influence of the viscosity of healthy and diseased human mucins on the motility of Helicobacter pylori.

The swimming strategies of unipolar flagellated bacteria are well known but little is known about how bipolar bacteria swim. Here we examine the motility of Helicobacter suis, a bipolar gastric-ulcer-causing bacterium that infects pigs and humans. Phase-contrast microscopy of unlabeled bacteria reveals flagella bundles in two conformations, extended away from the body (E) or flipped backwards and wrapped (W) around the body. We captured videos of the transition between these two states and observed three different swimming modes in broth: with one bundle rotating wrapped around the body and the other extended (EW), both extended (EE), and both wrapped (WW). Only EW and WW modes were seen in porcine gastric mucin. The EW mode displayed ballistic trajectories while the other two displayed superdiffusive random walk trajectories with slower swimming speeds. Separation into these two categories was also observed by tracking the mean square displacement of thousands of trajectories at lower magnification. Using the Method of Regularized Stokeslets we numerically calculate the swimming dynamics of these three different swimming modes and obtain good qualitative agreement with the measurements, including the decreased speed of the less frequent modes. Our results suggest that the extended bundle dominates the swimming dynamics.

Bipolar lophotrichous Helicobacter suis combine extended and wrapped flagella bundles to exhibit multiple modes of motility.

Recently, Farjas and Roura (FR) have proposed a universal scaling law to describe  crystallization kinetics based on a modification of the conventionally used Avrami model. In this letter, we apply the approach of Farjas and Roura to analyze the kinetics of an order-order phase transition in a diblock copolymer solution. We present an analysis of kinetics of the hexagonally packed cylinders (HEX) to gyroid transformation in polystyrene--polyisoprene (SI) diblock copolymer solutions in dimethyl phthalate using time-resolved small-angle X-ray scattering (SAXS) measurements. By shifting and scaling time in terms of the time at which the transformation rate is maximal, data for samples at two different concentrations at different ramp rates collapse onto the single universal curve predicted by Farjas and Roura. The activation energy for this process was estimated by fitting to the FR model. An estimate of the activation energy was also obtained by Avrami analysis of temperature jump experiments on the same sample. These two estimates differ by a factor of 2, suggesting that the two methods probe different stages of the phase transformation.

A Universal Scaling Analysis of Nonisothermal Kinetics in Block Copolymer Phase Transitions.

 spp., including the well-known human gastric pathogen , can cause gastric diseases in humans and other mammals. They are Gram-negative bacteria that colonize the gastric epithelium and use their multiple flagella to move across the protective gastric mucus layer. The flagella of different  spp. vary in their location and number. This review focuses on the swimming characteristics of different species with different flagellar architectures and cell shapes. All  spp. use a run-reverse-reorient mechanism to swim in aqueous solutions, as well as in gastric mucin. Comparisons of different strains and mutants of  varying in cell shape and the number of flagella show that their swimming speed increases with an increasing number of flagella and is somewhat enhanced with a helical cell body shape. The swimming mechanism of , which has bipolar flagella, is more complex than that of unipolar  exhibits multiple modes of flagellar orientation while swimming. The pH-dependent viscosity and gelation of gastric mucin significantly impact the motility of  spp. In the absence of urea, these bacteria do not swim in mucin gel at pH < 4, even though their flagellar bundle rotates.

Motility of Different Gastric  spp.

The gastric pathogen,  bacteria have to swim across a pH gradient from 2 to 7 in the mucus layer to colonize the gastric epithelium. Previous studies from our group have shown that porcine gastric mucin (PGM) gels at an acidic pH < 4, and  bacteria are unable to swim in the gel, although their flagella rotate. Changing pH impacts both the rheological properties of gastric mucin and also influences the proton (H+)-pumped flagellar motors of  as well as their anti-pH sensing receptors. To unravel these intertwined effects of acidic pH on both the viscoelastic properties of the mucin-based mucus as well as the flagellar motors and chemo-receptors of the bacterium, we compared the motility of  in PGM with that in Brucella broth (BB10) at different pH values using phase contrast microscopy to track the motion of the bacteria. The results show that the distribution of swimming speeds and other characteristics of the bacteria trajectories exhibit pH-dependent differences in both media. The swimming speed exhibits a peak at pH 4 in BB10, and a less pronounced peak at a higher pH of 5 in PGM. At all pH values, the bacteria swam faster and had a longer net displacement in BB10 compared to PGM. While the bacteria were stuck in PGM gels at pH < 4, they swam at these acidic pH values in BB10, although with reduced speed. Decreasing pH leads to a decreased fraction of motile bacteria, with a decreased contribution of the faster swimmers to the distributions of speeds and net displacement of trajectories. The body rotation rate is weakly dependent on pH in BB10, whereas in PGM bacteria that are immobilized in the low pH gel are capable of mechano-sensing and rotate faster. Bacteria can be stuck in the gel in various ways, including the flagella getting entangled in the fibers of the gel or the cell body being stuck to the gel. Our results show that in BB10, swimming is optimized at pH4, reflecting the combined effects of pH sensing by anti-pH tactic receptors and impact on H+ pumping of flagellar motors, while the increase in viscosity of PGM with decreasing pH and gelation below pH 4 lead to further reduction in swimming speed, with optimal swimming at pH 5 and immobilization of bacteria below pH 4.

Article	Year
Viscoelastic properties and dynamics of porcine gastric mucin. Biomacromolecules\| PubMed ID: 15877349	2005
Atomic force microscopy reveals aggregation of gastric mucin at low pH. Biomacromolecules\| PubMed ID: 16283779	2005
Electrolysis induces gradients and domain orientation in agarose gels. Physical review. E, Statistical, nonlinear, and soft matter physics\| PubMed ID: 16486143	2006
Kinetics of disorder-to-fcc phase transition via an intermediate bcc state. Physical review. E, Statistical, nonlinear, and soft matter physics\| PubMed ID: 16906856	2006
Rheology of gastric mucin exhibits a pH-dependent sol-gel transition. Biomacromolecules\| PubMed ID: 17402780	2007
Helicobacter pylori moves through mucus by reducing mucin viscoelasticity. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 19706518	2009
Kinetics of hexagonal cylinders to face-centered cubic spheres transition of triblock copolymer in selective solvent: Brownian dynamics simulation. The Journal of chemical physics\| PubMed ID: 20815592	2010
The Influence of Mucus Microstructure and Rheology in Helicobacter pylori Infection. Frontiers in immunology\| PubMed ID: 24133493	2013
Folding of pig gastric mucin non-glycosylated domains: a discrete molecular dynamics study. Journal of biological physics\| PubMed ID: 24615227	2012
Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments. Molecular microbiology\| PubMed ID: 26365708	2016
Helical and rod-shaped bacteria swim in helical trajectories with little additional propulsion from helical shape. Science advances\| PubMed ID: 28138539	2016
The biology of mucus: Composition, synthesis and organization. Advanced drug delivery reviews\| PubMed ID: 28970050	2018
Influence of the viscosity of healthy and diseased human mucins on the motility of Helicobacter pylori. Scientific reports\| PubMed ID: 29946149	2018
Bipolar lophotrichous Helicobacter suis combine extended and wrapped flagella bundles to exhibit multiple modes of motility. Scientific reports\| PubMed ID: 30258065	2018
A Universal Scaling Analysis of Nonisothermal Kinetics in Block Copolymer Phase Transitions. ACS macro letters\| PubMed ID: 35606962	2013
Motility of Different Gastric spp. Microorganisms\| PubMed ID: 36985208	2023
Unraveling the Intertwined Effect of pH on Motility and the Microrheology of the Mucin-Based Medium It Swims in. Microorganisms\| PubMed ID: 38004756	2023

Rama Bansil

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