This CAREER award by the Biomaterials program in the Materials Research Division to University of South Florida is to study combinatorial biomaterials that mimic the mechanical and chemical properties of the basement matrix for high throughput studies of endothelial cell mechanotransduction. Endothelial cells form the lining of blood vessels and other tissues by adhering to the basal lamina and organizing into monolayers. Due to the complex microenvironment of these specialized tissues, mechanotransduction (translation of mechanical inputs into biochemical signals) mechanisms are central to regulating endothelial cell homeostasis and progression towards disease states. A combinatorial approach is uniquely able to accurately recapitulate the range of natural physiology and rapidly analyze the interactions of multiple matrix-mediated mechanical and chemical signals in endothelial cell mechanobiology. The expected outcomes of the research program proposed here will provide the necessary tools and fill the gap in the current understanding of how mechanical properties and forces are sensed, translated into biochemical signals, and integrated with other pathways that control endothelial cell fate. Concurrently, hands-on tutorials, based on the underlying biophysical principles of mechanotransduction, will be developed for a high school Biomedical Sciences curriculum expected to encourage diversity in STEM disciplines. These tutorials will be designed and delivered by a team of high school students and teachers collaborating with University of South Florida faculty and graduate and undergraduate students. The proposed research and outreach activities will provide students opportunities to interact with researchers from a variety of disciplines and share their research with the community.
Endothelial cells organize on a thin protein matrix and form the lining of every blood vessel in the body. The present proposal integrates research and education activities designed to investigate the complex set of signals that direct the regulation and disease progression of these specialized tissues. Specifically, mechanisms of mechanotransduction (the process of translating mechanical inputs into biochemical signals) from forces caused by blood flow and tissue stiffness will be studied. A combinatorial approach will be used which enables high throughput studies to rapidly analyze the interactions of multiple mechanical and chemical signals. These studies will develop new combinatorial materials and are expected to provide an understanding of how mechanical properties and forces control endothelial cell behavior. Furthermore, the findings of this work will enable the design of materials that template the structure and guide the organization in engineered tissues for repair and replacement. Hands-on tutorials, based on the principles of mechanotransduction elucidated by this research, will be developed for a high school Biomedical Sciences curriculum expected to encourage diversity in STEM disciplines. These tutorials will be designed and delivered by a team of high school students and teachers collaborating with University of South Florida faculty and graduate and undergraduate students. This collaborative learning approach will enhance the training of students across multiple levels.
