The goal of this Faculty Early Career Development (CAREER) project is to (1) advance a conceptual framework for the mechanics of contraction in vascular smooth muscle (VSM) cells through nano-mechanical testing and computational modeling and (2) to create an educational program that incorporates nano-biomechanics and biomaterials with mechanical engineering learning. VSM cells form the middle layer in the walls of blood vessels and their contraction regulates vascular tone. The proposed experiments will characterize the structure-function relationships of the protein assemblies that form the contractile apparatus in VSM cells. The research will develop nano-biomechanical techniques that can measure the forces produced by the contractile apparatus under different loading conditions, external strains, and structural organization. The findings will be incorporated into a computational mechanochemical model based on first principles that ultimately arrives at the fundamental relationships.
The outcomes from this research will improve the analysis and design of biomaterials and tissue-engineered constructs used in cardiovascular repair by determining their effect on VSM contraction. The transformative aspect of this proposal is a methodology for cell mechanics that considers the role of subcellular mechanical factors. This methodology will be general enough to be translated to other smooth muscle and nonmuscle cell types. This proposal will build a learning pathway between engineering and the biomedical disciplines through an integrated research and teaching approach that will enrich the curriculum at the University of Washington. The planned outreach efforts will attract underrepresented K-12 students to engineering by exposing them to the unique interfaces that exist between biology and engineering. To complement this outreach, a virtual organization focused on biology and engineering at the nanoscale will be established in order to integrate the research and education of this proposal and to promote collaborations in the field of nano-biomechanics.