ACTIN-DEPENDENT CELL JUNCTION REINFORCEMENT UNDER EXTERNAL MECHANICAL STRESS

Abstract

The importance of large-scale actomyosin dynamics in cell junction formation and homeostasis has been previously outlined. However, the basis for stress-induced junction stabilization still awaits clarification. In this thesis, we developed a new method for localized stress application on single cell junction independent of cell-matrix interaction. When combined with custom quantitative 3D image analysis, it elucidates a mechanosensitive mechanism for external forces to reinforce junction complexes (adherens and tight junctions). Meanwhile, we noticed that cell junctions are locally stress-responsive, whereby junction polarization over the cell contact is triggered by an uneven distribution of mechanical tension. We then identified that, in polarized epithelial monolayer with established apical junctions, comparable external mechanical driving force exerted by the surroundings led to the recruitment of the tight junction complexes in a cadherins-insensitive manner. All of our observations are explained in the context of the mechanosensitive recruitment of actin, that serves as primary scaffolds at to recruit junctional components.