a-bead-movement-based-computational-framework-for-3-dimensional

A Bead Movement Based Computational Framework for 3-Dimensional Analysis of Biofilm Material Heterogeneity

Differences in the material properties of bacterial biofilms have been observed in biofilms of different bacterial species, within the same species under ...

Temple University

Generating realistic and complex computational domains for numerical simulations is often a challenging task. In neuroscientific research, more and more one-dimensional morphology data is becoming publicly available through databases. This data, however, only contains point and diameter information not suitable for detailed three-dimensional simulations. In this paper, we present a novel framework, AnaMorph, that automatically generates water-tight surface meshes from one-dimensional point-diameter files. These surface triangulations can be used to simulate the electrical and biochemical behavior of the underlying cell. In addition to morphology generation, AnaMorph also performs quality control of the semi-automatically reconstructed cells coming from anatomical reconstructions. This toolset allows an extension from the classical dimension-reduced modeling and simulation of cellular processes to a full three-dimensional and morphology-including method, leading to novel structure-function interplay studies in the medical field. The developed numerical methods can further be employed in other areas where complex geometries are an essential component of numerical simulations.

Generating Neuron Geometries for Detailed Three-Dimensional Simulations Using AnaMorph.

Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.

What Is Required for Neuronal Calcium Waves? A Numerical Parameter Study.

The endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca signaling. Our simulations, which account for Ca exchange on the plasma membrane and ER, show that spine ER needs to be present in distinct morphological conformations in order to overcome a barrier between the spine and dendritic shaft. We demonstrate that RyR-carrying spine ER promotes spine-to-dendrite Ca signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca communication, while maintaining aspects of Ca homeostasis in the spine head. Our work emphasizes the relevance of precise positioning of RyR-containing spine ER in regulating the strength and timing of spine Ca signaling, which could play an important role in tuning spine-to-dendrite Ca communication and homeostasis.

Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum.

Neuron classification is an important component in analyzing network structure and quantifying the effect of neuron topology on signal processing. Current quantification and classification approaches rely on morphology projection onto lower-dimensional spaces. In this paper a 3D visualization and quantification tool is presented. The Density Visualization Pipeline (DVP) computes, visualizes and quantifies the density distribution, i.e., the "mass" of interneurons. We use the DVP to characterize and classify a set of GABAergic interneurons. Classification of GABAergic interneurons is of crucial importance to understand on the one hand their various functions and on the other hand their ubiquitous appearance in the neocortex. 3D density map visualization and projection to the one-dimensional x, y, z subspaces show a clear distinction between the studied cells, based on these metrics. The DVP can be coupled to computational studies of the behavior of neurons and networks, in which network topology information is derived from DVP information. The DVP reads common neuromorphological file formats, e.g., Neurolucida XML files,  SWC files and plain ASCII files. Full 3D visualization and projections of the density to 1D and 2D manifolds are supported by the DVP. All routines are embedded within the visual programming IDE VRL-Studio for Java which allows the definition and rapid modification of analysis workflows.

Density Visualization Pipeline: A Tool for Cellular and Network Density Visualization and Analysis.

A dermal absorption model for small and macromolecules was previously proposed by Ibrahim et al. This model estimated absorption of therapeutics from the dermal tissue based on their molecular size and protein binding through blood and lymphatics. Blood absorption followed a two-pore theory and the lymphatic absorption was limited by the constant lymphatic flow rate. Current work builds on this steady-state concept by modeling the absorption from the dermis immediately after an injection is given (unsteady state). An injection in the dermis creates a localized pressure gradient which resolves itself over time. This phenomenon is captured in the model to estimate the impact of injection volume on the absorption rate constant. Blood absorption follows the two-pore theory but is time-dependent and the lymphatic absorption is determined based on valve opening and pressure driven convective flow, returning to steady-state as the molecule is absorbed. A direct comparison of the steady-state analysis, experimental data and the current model is made. The results indicate that accounting for the localized time-varying pressure can better predict the experimental absorption rate constants. This work significantly improves the existing understanding of macromolecule uptake from the interstitial fluid following intradermal injection.

Article	Year
Generating Neuron Geometries for Detailed Three-Dimensional Simulations Using AnaMorph. Neuroinformatics\| PubMed ID: 28447297	2017
What Is Required for Neuronal Calcium Waves? A Numerical Parameter Study. Journal of mathematical neuroscience\| PubMed ID: 30006849	2018
Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum. Scientific reports\| PubMed ID: 30353066	2018
Density Visualization Pipeline: A Tool for Cellular and Network Density Visualization and Analysis. Frontiers in computational neuroscience\| PubMed ID: 32676020	2020
Modeling Drug Absorption from the Dermis after an Injection. Journal of pharmaceutical sciences\| PubMed ID: 33248056	2021

Gillian Queisser

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