Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction
Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction
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DOI：
10.1038/s42003-020-01117-7
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发表时间：
2020-07-21
影响因子：
5.9
通讯作者：
Nain, Amrinder S.
中科院分区：
文献类型：
--
作者：
Padhi, Abinash;Singh, Karanpreet;Nain, Amrinder S.
对齐的细胞外基质纤维使成纤维细胞能够经历成肌纤维细胞活化并实现细长形状。活化的成纤维细胞能够收缩，使这些纤维的排列永久化。这种知之甚少的反馈过程在包括癌症在内的慢性纤维化疾病中至关重要。在这里，使用作为力传感器的纤维网络，我们确定了“3D垂直横向突起”（3D-PLPs），从横向细胞扩展名为缠绕演变。双股起源于穿过细胞的环状肌动蛋白波的分层，并在3D中自由摆动以接合相邻的纤维。一旦接合，板层形成并延伸多个次级缠绕，其填充以形成片状PLP，在将局部粘连转变为活化的（即，病理性）3D粘连。PLPs的特定形态使细胞能够增加平行纤维上的收缩性和力。控制细胞外网络的几何形状证实了各向异性的纤维环境支持3D-PLP的形成和功能，这表明了癌症相关的促纤维增生性扩张的解释。Padhi等人采用具有受控结构和排列的纳米纤维作为细胞外基质模型，他们研究了粘附成纤维细胞的力的施加。识别施加3D垂直横向突起的力，作者描述了导致平行相邻纤维收缩的机制，以及移动和对齐相邻纤维所需的力。这些发现与理解癌症相关的促结缔组织增生性扩张有关。
Aligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify "3D perpendicular lateral protrusions" (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion.Padhi et al. employ nanofibers with controlled structure and alignment as an extra-cellular matrix model, on which they study the exertion of forces from adherent fibroblasts. Identifying force exerting 3D perpendicular lateral protrusions, authors describe a mechanism which leads to the contraction of parallel, neighbouring fibers, and the forces needed to move and align the neighbouring fibers. These findings have relevance in understanding cancer-associated desmoplastic expansion.