Vascular Endothelial Cell Behavior in Complex Mechanical Microenvironments

The vascular mechanical microenvironment consists of a mixture of spatially and temporally changing mechanical forces. This exposes vascular endothelial cells to both hemodynamic forces (fluid flow, cyclic stretching, lateral pressure) and vessel forces (basement membrane mechanical and topographical properties). The vascular mechanical microenvironment is "complex" because these forces are dynamic and interrelated. Endothelial cells sense these forces through mechanosensory structures and transduce them into functional responses via mechanotransduction pathways, culminating in behavior directly affecting vascular health. Recent in vitro studies have shown that endothelial cells respond in nuanced and unique ways to combinations of hemodynamic and vessel forces as compared to any single mechanical force. Understanding the interactive effects of the complex mechanical microenvironment on vascular endothelial behavior offers the opportunity to design future biomaterials and biomedical devices from the bottom-up by engineering for the cellular response. This review describes and defines (1) the blood vessel structure, (2) the complex mechanical microenvironment of the vascular endothelium, (3) the process in which vascular endothelial cells sense mechanical forces, and (4) the effect of mechanical forces on vascular endothelial cells with specific attention to recent works investigating the influence of combinations of mechanical forces. We conclude this review by providing our perspective on how the field can move forward to elucidate the effects of the complex mechanical microenvironment on vascular endothelial cell behavior.