Forces During Cell Adhesion and Spreading: Implications for Cellular Homeostasis

Abstract

Cells adhere and spread by exerting forces against the cell membrane and against the extracellular matrix. Intracellular forces drive the membrane outward during spreading and stabilize cell shape in adherent and migrating cells. A balance of intracellular force with exogenous forces is required for maintenance of basic cell functions and cellular homeostasis. Here, we provide a multi-scale overview of the cellular machinery and intracellular forces at play during cell spreading and adhesion, including description at the molecular, cellular and tissue levels. We describe the cellular machinery required for force generation, explain aspects of its regulation, and show how the machinery operates to direct a cell to a homeostatic target. The biochemical and biophysical events that dominate the process of isotropic cell spreading are examined and the process of spreading is explained as a series of distinct phases, each with their own force signature. In addition, we consider how intracellular force affects mechanical cellular homeostasis and maintenance of tissue structure and function. The disruption of cellular mechanical homeostasis is described in the context of two prominent disease states: cancer and atherosclerosis.

Kinetic behaviour of the cells touching substrate: the interfacial stiffness guides cell spreading

“…During this process, the chemical reaction of actin polymerization is affected by integrin-ECM binding and membrane resisting. Without considering the network of filapodia or lamellipodia, isotropic spreading is studied here as the simplest form of this model34. We also ignored the capping proteins, nucleation proteins and other proteins which function in reactions of filaments35.…”

Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture

“…5C, panels i-ii). These results suggest that structural properties of 3D ECM such as fiber and pore size can selectively facilitate bipolar, uniaxial cell spreading, which may enable other biophysical cell behaviors that are closely linked to morphology, such as migration [49–51]. …”

Rasip1 mediates Rap1 regulation of Rho in endothelial barrier function through ArhGAP29

“…Activation of Rho results in increased activity of its effector Rho-associated protein kinase (ROCK), which phosphorylates myosin light chain 2 (MLC2) and myosin phosphatase targeting subunit 1 (MYPT1), resulting in increased actomyosin contraction. During the process of cell spreading, cell contraction must be reduced to allow cell spreading to occur (28,29). To assess whether Rap1 induces cell spreading by reducing cell contraction, A549-Epac1 cells, adherent to fibronectin, were stimulated with 007 for 30 min.…”