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Tension in the ranks: Cooperative cell contractions drive force-dependent collagen assembly in human fibroblast culture
Matter ( IF 18.9 ) Pub Date : 2024-02-16 , DOI: 10.1016/j.matt.2024.01.023
Alexandra A. Silverman , Jason D. Olszewski , Seyed Mohammad Siadat , Jeffrey W. Ruberti

Currently, there is no mechanistic model that fully explains the initial synthesis and organization of durable animal structure. As a result, our understanding of extracellular matrix (ECM) development and pathologies (e.g., persistent fibrosis) remains limited. Here, we identify and characterize cell-generated mechanical strains that direct the assembly of the ECM. Cell kinematics comprise cooperative retrograde “pulls” that organize and precipitate biopolymer structure along lines of tension. High-resolution optical microscopy revealed five unique classes of retrograde “pulls” that result in the production of filaments. Live-cell confocal imaging confirmed that retrograde pulls can directly cause the formation of fibronectin filaments that then colocalize with collagen aggregates exported from the cell, producing persistent elongated structures aligned with the direction of the tension. The findings suggest a new model for initial durable structure formation in animals. The results have important implications for ECM development and growth and life-threatening pathologies of the ECM, such as fibrosis.



中文翻译:

队伍中的紧张局势:细胞协作收缩驱动人成纤维细胞培养中依赖力的胶原蛋白组装

目前,还没有机制模型能够完全解释持久动物结构的初始合成和组织。因此,我们对细胞外基质(ECM)发育和病理学(例如持续性纤维化)的理解仍然有限。在这里,我们识别并表征了细胞产生的机械应变,这些机械应变指导 ECM 的组装。细胞运动学包括协同逆行“拉动”,沿着张力线组织和沉淀生物聚合物结构。高分辨率光学显微镜揭示了五种独特的逆行“拉力”,导致细丝的产生。活细胞共聚焦成像证实,逆向拉力可以直接导致纤连蛋白丝的形成,然后纤连蛋白丝与从细胞输出的胶原聚集体共定位,产生与张力方向一致的持久拉长结构。这些发现提出了动物初始持久结构形成的新模型。结果对 ECM 的发育和生长以及 ECM 的危及生命的病理学(例如纤维化)具有重要意义。

更新日期:2024-02-16
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