Speaker
Description
Curvature-dependent epithelial migration is usually described at the level of actin and adhesion, but recent experiments reveal a central role for organelle mechanics. We combine new experimental evidence on wound-edge geometry with a unified variational model of single-cell migration to argue that the endoplasmic reticulum (ER) acts as a mechanotransducer linking curvature, cytoskeletal forces and migration mode. In epithelial gaps, convex edges promote ER tubules, perpendicular focal adhesions and lamellipodial crawling, whereas concave edges promote ER sheets, parallel adhesions and purse-string-like contraction. Building on these findings, we formulate a thermodynamically consistent framework that couples ER sheet--tubule remodeling, membrane curvature elasticity, actin turnover, microtubule reorganization, intracellular flow, and cell polarity within a diffuse-interface description. The model explains how geometry and force bias intracellular organization through strain-energy minimization and predicts how perturbations of ER structure reshape polarity and motility. Together, this work provides a route toward a predictive theory of epithelial migration in which intracellular architecture is not a passive readout of mechanics, but an active regulator of cell movement.
Bibliography
@article{rawal2025edge,
title={Edge curvature drives endoplasmic reticulum reorganization and dictates epithelial migration mode},
author={Rawal, Simran and Keshavanarayana, Pradeep and Manoj, Diya and Khuntia, Purnati and Banerjee, Sanak and Thurakkal, Basil and Marwaha, Rituraj and Spill, Fabian and Das, Tamal},
journal={Nature Cell Biology},
volume={27},
number={10},
pages={1660--1675},
year={2025},
publisher={Nature Publishing Group UK London}
}
