Role of mechanobiology during epithelial and endothelial polarization and tubulogenesis

Prof. Venkantram Prasad Shastri (BIOSS and Institute for Macromolecular Chemistry, University of Freiburg)

Tubulogenesis, the organization of cells into tubular structures and lumens is a complex process that involves a series of well orchestrated signaling and organizational steps.  In endothelial cells, their organization into lumens requires apical-basal polarization.  The polarization of cell involves discrete localization of proteins, which is necessary not only for organization of cells into tubes and their subsequent maturation, but also to define the basal and luminal surface. Although, some of the soluble signals that favor such tissue morphogenesis have been identified, recapitulating these events ex vivo has been challenging. The objective of this project is to understand the role of material mechanics in the presentation of soluble signals and activation of signal cascades in tubulogenesis.  Using synthetic extracellular matrices (ECM) with well-defined mechanical properties and chemistry, the changes to gene expression and signaling will be followed to identify key parameters necessary for the induction of phenotypic changes necessary for tubulogenesis. An understanding of how ECM stiffness directs the interplay between bound and soluble signals is expected to result in a mechanobiology solution to organogenesis.