文章基本信息

标题：Tension-dependent stabilization of E-cadherin limits cell–cell contact expansion in zebrafish germ-layer progenitor cells
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作者：Jana Slováková ; Mateusz Sikora ; Feyza Nur Arslan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：8
DOI：10.1073/pnas.2122030119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Cell–cell contact formation is a key step in the evolution of multicellularity. While the molecular and cellular processes underlying cell–cell adhesion and contact formation have been extensively studied, comparably little is known about the physical principles guiding these processes. Actomyosin cortex tension differentially applied at the cell–cell and cell–medium interfaces was shown to promote expansion of the cell–cell contacts. Here, we uncover a nonlinear relationship between cortex tension and cell–cell contact size; in a low-tension regime, cell–cell contact size positively scales with cortex tension, while the high-tension regime promotes small contacts. This change in behavior is due to tension decreasing the turnover of adhesion molecules at the cell–cell contact, limiting contact expansion. Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact.
关键词：encell adhesioncell–cell contact formationmechanosensing