MECHANICAL IMPACT OF APOPTOTIC CELL EXTRUSION ON NEIGHBOURING TISSUE

Abstract

Forces from apoptosis generated by the release of tissue pre-tension were found to propagate from dying cell to about two rows of neighbouring cells. Concurrent gap closure during cell extrusion induced stretching of neighbouring cells. In response to tissue stretching, spatial inhomogeneity in mechanotransduction arose for growth-promoting mechanosensitive YAP and ERK2 in neighbouring cells. Similar spatial inhomogeneity was also observed for neighbouring cells undergoing cell division. Moreover, neighbouring cells within the first two rows showed significantly higher frequency of cell division events and shorter synthesis phase of interphase to cytokinesis transition. In an extension to this study, the inhomogeneous mechanotransduction was shown to emerge from a combination of non-uniform nuclear size distribution and non-uniform pattern of mechanical force applied to the neighboring cells upon apoptosis. This study showed how neighbouring tissue responded to mechanics of apoptosis which complemented with current biochemical understanding of compensatory tissue growth to maintain tissue homeostasis.