Responses of epithelial monolayers to an imposed deformation

Epithelial monolayers are a class of animal tissue which comprise some of the most basic and important structures in metazoans. Many remarkable morphogenetic events, responsible for determining adult tissue shape, take place in epithelia and they continue to perform crucial functions throughout adult life. Whether it is the filling of the bladder or during a precise morphogenetic transformation, epithelia must frequently undergo or drive tissue deformations. Therefore, much effort has been directed towards understanding the combination of material properties and cellular behaviours which determine how epithelia respond to the application of stress and strain. The complex biophysical environment of in vivo tissues, however, can hinder attempts to understand the underlying mechanisms and principles at play. To address this, a novel and highly simplified system is utilised in which uniaxial strain is applied to epithelia monolayers which are devoid of a substrate. Application of compressive strain to these suspended epithelia unexpectedly revealed their ability to autonomously flatten buckles and remodel cell shape as the tissue mechanically adapts to a new shorter length over a duration of ~60 seconds. These changes, which are found to be driven by actomyosin contractility, appear fully reversible since the epithelia can readapt to their initial length when it is restored and maintained over a similar time period. At longer timescales, cell division within the epithelia is also found to be affected by the application of strain. Both compressive and tensile strain causes an alignment of division orientation which is demonstrated to be due to a global realignment of cell long axes combined with orientation of division along these axes, rather than by cells detecting and responding to long-range tissue stress orientation. In turn, these strain-oriented cell divisions homeostatically alter tissue organisation by redistributing cell mass along the direction of division and ultimately restore isotropic cell shape