The interplay of membrane cholesterol and substrate on vascular smooth muscle biomechanics

Abstract

Cardiovascular disease (CVD) remains the primary cause of death worldwide. Specifically, atherosclerosis is a CVD characterized as a slow progressing chronic inflammatory disease. During atherosclerosis, vascular walls accumulate cholesterol and cause fatty streak formation. The progressive changes in vascular wall stiffness exert alternating mechanical cues on vascular smooth muscle cells (VSMCs). The detachment of VSMCs in the media layer of the vessel and migration toward the intima is a critical step in atherosclerosis. VSMC phenotypic switching is a complicated process that modifies VSMC structure and biomechanical function. These changes affect the expression and function of cell adhesion molecules, thus impacting VSMC migration. Accumulating evidence has shown cholesterol is capable of regulating cellular migration, proliferation, and spreading. However, the interaction and coordinated effects of both cellular cholesterol and the extracellular matrix (ECM) stiffness/composition on VSMC biomechanics remains to be elucidated.

Keywords: Atherosclerosis; Atomic force microscopy; Cell mechanics; Cholesterol; Cytoskeleton; Substrate stiffness; Vascular smooth muscle cells.