Tissue morphogenesis arises from the culmination of changes in cell-cell junction length. Mechanochemical signaling in the form of RhoA underlies these ratcheted contractions, which occur asymmetrically. The underlying mechanisms of asymmetry remain unknown. We use optogenetically controlled RhoA in model epithelia together with biophysical modeling to uncover the mechanism lending to asymmetric vertex motion. Using optogenetic and pharmacological approaches, we find that both local and global RhoA activation can drive asymmetric junction contraction in the absence of tissue-scale patterning. We find that standard vertex models with homogeneous junction properties are insufficient to recapitulate the observed junction dynamics. Furthermore, these experiments reveal a local coupling of RhoA activation with E-cadherin accumulation. This motivates a coupling of RhoA-mediated increases in tension and E-cadherin-mediated adhesion strengthening. We then demonstrate that incorporating this force-sensitive adhesion strengthening into a continuum model is successful in capturing the observed junction dynamics. Thus, we find that a force-dependent intercellular "clutch" at tricellular vertices stabilizes vertex motion under increasing tension and is sufficient to generate asymmetries in junction contraction.
Keywords: RhoA, optogenetics, adhesion clutch, junction mechanics.
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