BME Colloquium Series: Cynthia A. Reinhart-King, Ph.D.

Mechano-Chemical Regulation of Endothelial Cell Behavior

The cellular microenvironment is a complex balance of chemical and mechanical factors which mediate fundamental cell behaviors, including adhesion and migration. Work in the Reinhart-King Lab focuses on describing governing parameters that mediate endothelial cell-biomaterial interactions at the molecular, cellular and tissue scales. Endothelial cells comprise the nearly impermeable single cell barrier that lines the lumen of all blood vessels. Physiologically, blood vessel formation is important for wound healing; however, aberrant endothelial cell behavior can lead to tumor formation and numerous vascular diseases including atherosclerosis. Using materials of well-characterized chemical and mechanical properties which mimic the in vivo environment, we have characterized fundamental mechanisms of endothelial cell adhesion, spreading, and migration as a function of matrix compliance and chemistry. We have implemented Traction Force Microscopy, a powerful tool that quantifies the magnitude, direction and location of cellular traction stresses, to investigate individual endothelial cell mechanics in response to various extracellular matrix cues. I will discuss our approach to decipher the complex balance between material chemistry and mechanics, and describe our insights into the mechano-chemical regulation of endothelial cell physiology. Interestingly, we have found that endothelial cell assembly varies based on substrate mechanics. Moreover, we showed for the first time that endothelial cells are able to communicate mechanically through their substrate using contractile forces. Such insights into the mechanics of endothelial cell behavior will enable rational design of tissue-engineered therapeutics and a greater understanding of how perturbations in the cellular microenvironment lead to disease progression.