Cell-Generated Forces in Tissue Assembly, Function, and Disease

While the cell and tissue-level effects of exogenous, physiological forces like shear stress and pressure are well-documented, the effects of endogenous cell-generated forces and the mechanics of the microenvironment have only recently gained significant attention. There is now mounting evidence that cells generate contractile forces that can elicit changes in the balance between cell-cell cohesion and cell-matrix adhesion within tissues. This balance is critical in governing tissue structure, formation and health. These cell-generated traction forces are altered by changes in the mechanics of the cellular microenvironment. Notably, changes in tissue stiffness accompany both the progression of many diseases including atherosclerosis, heart disease and cancer, and in normal physiological processes including development. Recent evidence suggests that the mechanics of the microenvironment may play a role in dictating cell function and tissue structure. Additionally, abnormal changes in tissue stiffness may promote disease progression. This chapter will discuss the role of cell-mediated forces and the mechanics of the microenvironment in the assembly and maintenance of cells into tissues. Recent advances in tools, techniques, and materials used to study cellular forces and the effects of matrix mechanics will be described. Additionally, the role of cellular traction forces and matrix mechanics in both normal and diseased states will be described, using examples primarily from the cardiovascular system to illustrate the relationship between mechanics and cell and tissue function.