Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling

Cells of the myocardium are at home in one of the most mechanically dynamic environments in the body. At the cellular level, pulsatile stimuli of chamber filling and emptying are experienced as cyclic strains (relative deformation) and stresses (force per unit area). The intrinsic characteristics of tension-generating myocytes and fibroblasts thus have a continuous mechanical interplay with their extrinsic surroundings. This review explores the ways that the micromechanics at the scale of single cardiac myocytes and fibroblasts have been measured, modeled, and recapitulated in vitro in the context of adaptation. Both types of cardiac cells respond to externally applied strain, and many of the intracellular mechanosensing pathways have been identified with the careful manipulation of experimental variables. In addition to strain, the extent of loading in myocytes and fibroblasts is also regulated by cues from the microenvironment such as substrate surface chemistry, stiffness, and topography. Combinations of these structural cues in three dimensions are needed to mimic the micromechanical complexity derived from the extracellular matrix of the developing, healthy, or pathophysiologic heart. An understanding of cardiac cell micromechanics can therefore inform the design and composition of tissue engineering scaffolds or stem cell niches for future applications in regenerative medicine.