Cell focal adhesion clustering leads to decreased and homogenized basal strains.

The subendothelial matrix of the artery is a complex mechanical environment where endothelial cells respond to and affect changes upon the underlying substrate. Our recent work has demonstrated that endothelial cell strain heterogeneity increases on a more heterogeneous underlying subendothelial matrix, and these cells display increased focal adhesion presence on stiffer substrate areas. However, the impact of these grouped focal adhesions on endothelial cell strains has not been explored. Here, we use finite element modeling to investigate the effects of microscale stiffness heterogeneities and focal adhesion location and stiffness on endothelial cell strains. Shear stress applied to the apical cell layer demonstrated a minimal effect on cell strain values, while substrate stretch had a greater effect on cell strain in the cell-substrate model. The addition of focal adhesions into the computational model (cell-FA-substrate model) predicted a decrease and homogenization of the cell strains. For simulations including focal adhesions, stiffer and more distributed adhesions caused increased and more heterogeneous endothelial cell strains. Overall, our data indicate that cells may group focal adhesions to minimize and homogenize their basal strains.