Ndiaye Anne-Betty, Koenderink Gijsje H, Shemesh Michal
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, Netherlands.
Front Cell Dev Biol. 2022 Apr 11;10:882037. doi: 10.3389/fcell.2022.882037. eCollection 2022.
The mammalian cytoskeleton forms a mechanical continuum that spans across the cell, connecting the cell surface to the nucleus transmembrane protein complexes in the plasma and nuclear membranes. It transmits extracellular forces to the cell interior, providing mechanical cues that influence cellular decisions, but also actively generates intracellular forces, enabling the cell to probe and remodel its tissue microenvironment. Cells adapt their gene expression profile and morphology to external cues provided by the matrix and adjacent cells as well as to cell-intrinsic changes in cytoplasmic and nuclear volume. The cytoskeleton is a complex filamentous network of three interpenetrating structural proteins: actin, microtubules, and intermediate filaments. Traditionally the actin cytoskeleton is considered the main contributor to mechanosensitivity. This view is now shifting owing to the mounting evidence that the three cytoskeletal filaments have interdependent functions due to cytoskeletal crosstalk, with intermediate filaments taking a central role. In this Mini Review we discuss how cytoskeletal crosstalk confers mechanosensitivity to cells and tissues, with a particular focus on the role of intermediate filaments. We propose a view of the cytoskeleton as a composite structure, in which cytoskeletal crosstalk regulates the local stability and organization of all three filament families at the sub-cellular scale, cytoskeletal mechanics at the cellular scale, and cell adaptation to external cues at the tissue scale.
哺乳动物的细胞骨架形成了一个跨越细胞的机械连续体，将细胞表面与质膜和核膜中的细胞核跨膜蛋白复合物相连。它将细胞外的力传递到细胞内部，提供影响细胞决策的机械信号，同时也能主动产生细胞内力，使细胞能够探测和重塑其组织微环境。细胞会根据基质和相邻细胞提供的外部信号以及细胞质和细胞核体积的细胞内源性变化来调整其基因表达谱和形态。细胞骨架是一个由三种相互贯穿的结构蛋白组成的复杂丝状网络：肌动蛋白、微管和中间丝。传统上，肌动蛋白细胞骨架被认为是机械敏感性的主要贡献者。现在这种观点正在转变，因为越来越多的证据表明，由于细胞骨架的串扰，这三种细胞骨架丝具有相互依赖的功能，其中中间丝起着核心作用。在本综述中，我们讨论了细胞骨架串扰如何赋予细胞和组织机械敏感性，特别关注中间丝的作用。我们提出了一种将细胞骨架视为复合结构的观点，其中细胞骨架串扰在亚细胞尺度上调节所有三个丝家族的局部稳定性和组织，在细胞尺度上调节细胞骨架力学，在组织尺度上调节细胞对外部信号的适应。
