Events
Department of Mathematics and Statistics
Texas Tech University
PDF abstract
Extracellular matrix (ECM) is a key part of the cellular microenvironment and critical in multiple disease and developmental processes. Representing ECM and cell-ECM interactions is a challenging multi-scale problem that acts across both the tissue and individual cell levels. While several computational frameworks exist for ECM modeling, they often focus on either very detailed modeling of individual ECM fibers or only a single aspect of the ECM and in both cases are often computationally unscalable. In this presentation, using the PhysiCell agent-based modeling platform, we combine aspects of previous modeling efforts and develop a framework of intermediate detail that addresses direct cell-ECM interactions. We accomplish this using a three-variable representation of ECM — anisotropy, density, and orientation — and place these elements of ECM throughout space. Cells alter their motility in response to the local ECM variables and remodel ECM based on their velocity. With stepwise introduction of the framework features, we show a wide range of cell actions and ECM patterns that can be created. We then demonstrate this framework with a model of cancer cell invasion where the cell’s motile phenotype is driven by the ECM microstructure that is patterned by prior cell motility. When paired with the ECM, the cell invasion model captures a diverse range of tissue-level behaviors — from recapitulating a homeostatic tissue, to indirect communication of paths (stigmergy), to collective migration. This result suggests that cell-cell communication mitigated via the ECM enables and constitutes an important mechanism for pattern formation in dynamic cellular patterning. Finally, we talk generally about the tissue microenvironment, cell-cell interactions, and the use of agent-based models to explore and hypothesize explanations of those dynamics.
Zoom link:
https://texastech.zoom.us/j/94471029838?pwd=ZlJXR2JhU0ZjUHhYOUlmVGN3VFFJUT09