The Role of Global and Local Mechanical Signals in Modulating Cell Spreading

Abstract

Cell spreading on a flat surface is controlled by the interaction of cell adhesion, actin-based cellular deformations, and intracellular stresses. It has been shown that many cell types obtain larger spread areas on stiffer substrates [1]. We present a 2D model and finite element simulations of a spreading cell interacting with a deformable substrate through focal adhesion complexes. Focal adhesion complexes are modeled by collections of linear springs that depend on local concentrations of a ligand-activated bound integrin and can form and break dynamically in a stress and strain dependent manner. The cell is treated as a hypoelastic material that undergoes active deformations that represent cell spreading. By considering various formulations for the active deformation, which is characterized by an active rate of deformation tensor field, we use this model to better understand whether the mechanism of cell spreading is localized or governed by a global signal. Specifically, we consider the ability of a cell to integrate local signals and define an active rate of deformation that depends on the cell-level integration of signals arising from bound integrin concentrations, which enhance cell spreading, and from intracellular tension, which inhibit cell spreading. We also consider a spatially inhomogeneous active rate of deformation field that depends on local values of bound integrin concentrations and intracellular tension. We find that cell spread areas are governed by a combination of global signal integration, which accounts for long-range communication within a cell, and local integrin binding and tensile stress. It is this combination of signaling mechanisms that allows us to obtain experimentally observed cell spread area dependence on substrate stiffness.[1] Yeung, T. et al. “Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion.” Cell Motility and the Cytoskeleton 60 (2005): 24-34.