BRITE Pivot: Engineered Extracellular Matrix Cues Affecting Endothelial Phenotypic Change

Blood vessel cells known as endothelial cells can change to another type of cell and contribute to vascular disease. This change is associated with plaque formation within atherosclerotic vessels. A key component of blood vessels is the underlying scaffolding structure that provides physical support and instructs endothelial cells. It isn't known if the small-scale molecular structure of the blood vessel affects the changes in cell type. This Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Pivot award supports research to discover new knowledge of how the mechanical properties of the scaffolding structure influence endothelial fate. The findings from this award may influence the design of new therapies to treat vascular diseases. Therefore, the findings from this award will benefit our society by advancing national health. The educational activities promote the development of military veteran college students from underserved communities through lectures, laboratory training, and summer research experiences that broaden participation in scientific research. Endothelial-mesenchymal transition is a biological process in which vascular endothelial cells acquire a mesenchymal identity. This transition is involved in cardiovascular diseases such as atherosclerosis, in which endothelial cells give rise to smooth muscle-like cells within the plaque lesion. How the biochemical and biomechanical cues from the extracellular matrix milieu influences this transition is largely unknown. The project will engineer microenvironments composed of combinatorial extracellular matrix proteins to model that of atherosclerotic plaques in which this transition takes place. The research objective is to apply multivariate experimental design and analysis to quantify the role and interaction effects among extracellular matrix components and shear stress on endothelial-mesenchymal transition. Through this award, a deeper research program focused on vascular mechanobiology in both technology development as well in the application of single-cell transcriptomics and multifactorial analysis, will be achieved. This award will form the foundation of a new research trajectory focusing on the mechanobiology of extracellular matrix interactions for improved understanding of cardiovascular disease progression. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.