The major goal of this CAREER proposal is to investigate mechanical force-mediated biomechanical responses of vascular smooth muscle cells, a key player in the context of mechanically exacerbated vascular diseases. Although there have been studies characterizing cellular responses of vascular smooth muscle cells to mechanical stimuli, the precise mechanical characteristics of their responses (including their innate contraction and cell stiffness modulation) remains largely elusive and uncharacterized. Given the critical involvements of contraction and mechanical stiffness modulations of vascular smooth muscle cells in regulating hypertension-induced vascular pathologies, our research is set out to specifically address this critical knowledge gap by leveraging our demonstrated expertise in microfabrication and cell mechanics to generate novel micromechanical tools to investigate force-mediated biomechanical phenotypic changes of vascular smooth muscle cells.
Biomechanical changes in vascular smooth muscle cell contraction and cell stiffness play an important functional role in regulating adaptation and remodeling of vessel walls in hypertension. Thus, a better understanding of the intimate interaction between external forces and changes in biomechanical properties of vascular smooth muscle cells will provide critical insights into how vascular smooth muscle cells transduce these forces and ultimately pave the way to developing drugs that specifically interfere with pressure-induced vascular pathologies. As an integral part of this CAREER proposal, a comprehensive education plan will be developed to target students from different educational levels and genders and ethnicities. Technologies developed in the context of this CAREER proposal will be used as vehicles for outreach activities targeting K-12 students in Ann Arbor and Ypsilanti school districts. We will develop educational modules aimed at altering preconceptions of science and engineering held by K-12 students. A new interdisciplinary course in Biomechanics will also be developed as an outcome of this CAREER proposal.
