Gubbala, U. R. | Search bioRxiv

bioRxiv2026

Differential turnover of apicobasal regulators drives emergent mechano-response and shape homeostasis

Epithelial cell shape plays a fundamental role in tissue dynamics. Numerous studies have established how cells drastically change their shape to promote epithelial tissue morphogenesis. However, the mechanisms enabling cells to maintain their shape remain far less understood. Here, leveraging live imaging in Drosophila epithelial tissue and theoretical modeling, we identify an emergent mechano-chemical feedback that ensures junction length and cell shape stability, without requiring a dedicated molecular force sensor. We find that an increase in junction length is associated with a passive dilution of E-Cadherin, followed by an increase in Myosin-II-dependent contractility that reduces junction length. Theoretically, we show that this regulation of junction length generically emerges when negative and positive regulators of contractility have distinct kinetics. Experiments confirm that E-Cadherin acts as a negative regulator with slow turnover. Mechanistically, local dilution of E-Cadherin passively lifts an inhibition on lateral apicobasal polarity components, allowing the RhoGEF Cyst -- with its fast turnover -- to accumulate and increase contractility. Perturbing this feedback results in aberrant cell junction and shape regulation, thereby compromising the ability of the tissue to buffer local mechanical fluctuations and global mechanical stresses. Altogether, we propose that differential turnover between apical and lateral polarity complexes provides an emergent mechano-response for junction length and cell shape homeostasis.

biophysics↗

bioRxiv2026

Logic of optimal collective migration in heterogeneous tissues

Collective cell migration is a critical process in embryogenesis and cancer invasion. Recent work has shown that uniform tissues can undergo sharp rheological transitions, with collective motion emerging above a critical cell motility. In vivo, however, migration typically involves multiple populations with distinct motile and adhesive properties, and how this heterogeneity shapes collective dynamics remains unclear. Here, using two different vertex model implementations, we show that migration of heterogeneous clusters through tissues is maximized at intermediate adhesion strength: too little and the cluster fragments, too much and cluster cell cohesion suppresses the rearrangements needed for forward motion. We test our model against recent and new data on zebrafish mesendoderm invasion, where graded Nodal signalling regulates both motility and adhesion differences. By mapping measured Nodal levels to mechanical parameters, the model not only reproduces migration outcomes across homogeneous and heterogeneous clusters, but also discriminates between alternative adhesion rules. Strikingly, the inferred parameters place the system near the predicted optimum, where adhesion is strong enough to maintain cohesion yet graded enough to allow selective coupling among heterogeneous neighbors. These results identify an optimal balance between cohesion and interfacial remodeling as a general principle coordinating collective invasion in heterogeneous tissues. Significance statementCells often migrate collectively during embryonic development and cancer invasion, but tissues are rarely uniform and different cells differ both in their adhesion and activity. Using models of tissue mechanics, we show that collective invasion is maximized at an intermediate level of adhesion within the migrating cluster cells: too little and the cluster falls apart, too much and it cannot advance. We test this principle against experiments in zebrafish gastrulation, where a signaling gradient simultaneously controls both cell motility and adhesion. The model reproduces migration outcomes across a range of experiments and identifies the adhesion rule cells use to selectively stick to neighbors. These results reveal a simple mechanical logic for how heterogeneous cell collectives coordinate invasion.

biophysics↗