Controlling Epithelial Cell Shape

I will discuss my lab’s recent work to study the biophysical mechanisms regulating control of cell shape in epithelial tissue. In particular, we have used optogenetics to locally regulate Rho activity at cell junctions to uncover how local Rho pulses drive junction contraction and stabilization via a ratcheting mechanism. We find that at short timescales, Rho activation drives junction contraction that reverses upon Rho reduction. Sustained RhoA activity shows a similar initial rapid contraction followed by a slow contractile phase. Upon removal of RhoA activation, the junction does not fully recover back to its original length, similar to junctional ratcheting observed in vivo. We find that this ratchet is dependent on both trans E-cadherin interactions and Formin activity. To understand these data, we model junction length in response to variable tension. In contrast to existing vertex models, our data argues that a junction has a rest length that is determined by the force-dependent junctional remodeling under acute periods of tension. This model then predicts that the slow contractile phase will eventually saturate to limit the amount of junction length changes and this is indeed what we see experimentally. We can overcome this saturation by inducing multiple activation periods, recapitulating junctional ratcheting seen in vivo. Altogether, these data provide insight into the underlying molecular and biophysical mechanisms of junction length changes seen in development.