The research objective of this Faculty Early Career Development (CAREER) award is to use a combination of micro-fabrication, live cell imaging, molecular assay, traction force measurement, and mathematical modeling to elucidate the biomechanical and biochemical mechanisms for epithelial chiral morphogenesis on micopatterned surfaces. Chirality, also known as handedness or left-right (LR) asymmetry, is well conserved in the development of living organisms. In vertebrate development, the formation of epithelial chiral structures (i.e., chiral morphogenesis) is biomechanically important in establishing the LR asymmetric body plan. Recently, we have recapitulated such chiral morphogenesis on micropatterned surfaces. Studies conducted under this award will evaluate the role of cell biomechanics in micropatterned cell chirality with experiments and numerical simulation, with the emphasis on single cell chirality and the effects of cell-cell interactions. In addition, important signaling pathways and cytoskeletal proteins will be identified and analyzed for their effects on epithelial chirality and cell mechanics. This project presents a comprehensive effort to understand the biomechanical and biomolecular mechanisms of patterned epithelial chiral morphogenesis, which reflects a fundamental yet poorly understood cellular property and may directly relate to asymmetry in development and disease. If successful, the proposed research will (1) develop a new conceptual framework to study the chirality of cellular collective behaviors; (2) address the role of intracellular and intercellular mechanisms in determining multi-cellular LR asymmetry; and (3) initiate a new paradigm in research of LR asymmetry in development and diseases with an in vitro multicellular system. The educational plan focuses on course development in Cell Biomechanics at the undergraduate and graduate level as well as the outreach involving high school and undergraduate students. In addition, new initiatives will involve the development of artistic works to inform students and the general public of the importance of LR asymmetry in development and disease.
