Reversible superdeformability of hiPSC epithelial cortinoids

• 成果类型: Article
• 署名作者: Jana, Anirban; Tauber, Justin; Boyreau, Adeline; Gurchenkov, Basile; Recher, Gaelle; Feyeux, Maxime; Alessandri, Kevin; Nassoy, Pierre; Mahadevan, L.
• 署名单位: Universite de Bordeaux; Harvard University; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - Institute of Physics (INP); Harvard University; Harvard University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2528603123
• 发表日期: 2026-05-26
• 页码: e2528603123
• 关键词: pluripotency; superdeformability; epithelia; organoids; mechanical buffer; HYDROGEL MICROCAPSULES; stem-cells; culture; morphogenesis; mechanics

摘要

Epithelial cortinoids, fluid-filled shells formed from induced pluripotent stem cells (iPSCs), must accommodate large deformations during growth and morphogenesis. Using inflation-deflation assays and high-resolution imaging, we find that these fluid-filled shells are weakly pressurized and achieve extreme deformability through reversible soft modes of deformation accommodated by the cytoskeleton. We show that cytoskeletal elements such as actin localized along lateral cell edges undergo tilt and bend instabilities that buffer mechanical load by decoupling apico-basal stretching from lateral extension. These reversible instabilities act as elastic safety valves, permitting large shape changes without loss of epithelial hydraulic and topological integrity. A minimal theoretical and computational model demonstrates how tilt and bend reduce effective resistance to radial thinning and explains the observed pressure-strain softening. Thus, iPSC shells exploit reversible cytoskeletal instabilities as mechanical buffers, enabling robust tolerance of large deformations in developing epithelia.