concentric-gel-system-to-study-biophysical-role-matrix

Concentric Gel System to Study the Biophysical Role of Matrix Microenvironment on 3D Cell Migration

The ability of cells to migrate is crucial in a wide variety of cell functions throughout life&#160;from embryonic development and wound healing&#160;to ...

FOM Institute AMOLF

The microstructural basis of the characteristic nonlinear mechanics of biopolymer networks remains unclear. We present a 3D network model of realistic, cross-linked semiflexible fibers to study strain-stiffening and the effect of fiber volume-occupancy. We identify two structural parameters, namely, network connectivity and fiber entanglements, that fully govern the nonlinear response from small to large strains. The results also reveal distinct deformation mechanisms at different length scales and, in particular, the contributions of heterogeneity at short length scales.

The role of structure in the nonlinear mechanics of cross-linked semiflexible polymer networks.

Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.

Article	Year
The role of structure in the nonlinear mechanics of cross-linked semiflexible polymer networks. The Journal of chemical physics\| PubMed ID: 22360221	2012
Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy. Journal of the Royal Society, Interface / the Royal Society\| PubMed ID: 25100319	2014

Nicholas Agung Kurniawan

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