Mechanical Interaction between Cells and Extra Cellular Matrix
Doctor of Philosophy
The mechanical interactions between Cells and Extracellular Matrix (ECM) play a central role in various cellular processes including motility, differentiation, shape change and wound healing. Contracting cells actively pull the surrounding ECM and cause its remodeling. At the same time, the remodeled ECM in turn regulates both cell mechanical behavior and gene expression. To understand ECM remodeling and its impact on cell regulation, we first construct two continuum theories, a Landau-type theory and a scaling law-type theory, to understand the nonlinear elasticity of ECM. The former elucidates the relation between fiber alignment and nonlinear elasticity, while the later generalizes previous scaling laws and reveals new mechanical regimes in the phase diagram. Next, we build an elastic model, which explicitly includes both cells and collagen fibers, to explore the micromechanics of cellularized ECM on the scale of cell size. It shows that contracting cells remodel the micromechanics of their surrounding ECM in a strain and distance-dependent manner. Finally, we introduce the viscoelastic feature into this model and show viscoelasticity is essential in ECM remodeling. This work provides a platform to study Cell-ECM interactions regulated cell motility and it potentially serves as a guide for experimental work.
Cell-ECM interaction; micromechanics; continuum nonlinear elastic theory; discrete model; viscoelasticity