Generating active T1 transitions through mechanochemical feedback

2021 
Convergence-extension is a morphological process involved in the shaping of complex biological tissues. It is driven by an intricate interplay of cellular behaviours carefully controlled by chemical and mechanical signalling. A key cellular process in convergence-extension is intercalation, i.e. the exchange of cell neighbours via T1 transitions. Here we construct and analyse a model with positive feedback between recruitment of force-generating molecules and mechanical tension in cell junctions. The model characterises an important class of active T1 events, which occur against locally imposed mechanical stresses, as a function of a pulling force applied to the tissue boundary, characteristic time scales of viscoelastic remodelling in cell junctions, and kinetics of myosin motors. Furthermore, we measured the time scale associated with T1 events, and used local strain, cell shapes, and polarisation of myosin motors to show the formation of tension chains and alignment of junctions in the direction of intercalation. Using a minimal setup of several active cells embedded in an otherwise passive tissue, we found an optimal range of applied external pulling forces that activate the cell's contractile machinery and induce an active T1 transition. This initiates local convergence-extension flows that extend the tissue perpendicular to the direction of the maximum principal applied stress and provides an important cellular mechanism for tissue-scale remodelling, e.g. as observed during primitive streak formation in avian embryos.
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