Role of cell-matrix mechanical communication during lumen formation

Lumen formation is a critical step in embryonic development. Nearly all metazoans contain internal cavities (lumens) lined by a layer of epithelial cells that serve to isolate cellular and tissue functions. While the basal extracellular matrix (bECM) plays an important role in cell polarization and lumen positioning during lumenogenesis, little is known about how mechanical properties of the bECM interact with focal adhesion signaling to balance external and cell-generated cytoskeletal forces during lumen formation and expansion. We developed optogenetic tools based on the iLID-SspB dimer to manipulate focal adhesion activity. We stably integrated these tools into epithelial cell lines (MDCKs) to precisely control focal adhesion formation and activity during lumenogenesis in 3D environments with different mechanical properties. We find that stiffer bECMs result in lumens of higher dimensions and sphericity. By combining optogenetic manipulation of cell-ECM mechanical signaling with finite element modeling of ECM deformation, we aim to understand how different bECM mechanical properties interact and feedback with active cell focal adhesion signaling and cytoskeleton to precisely regulate lumen formation, shape, and expansion.