非肌球蛋白 II 异构体在细胞形态动力学过程中建立张力和弹性中的独特作用。
Distinct roles of nonmuscle myosin II isoforms for establishing tension and elasticity during cell morphodynamics.
机构信息
Zoological Institute, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
出版信息
Elife. 2021 Aug 10;10:e71888. doi: 10.7554/eLife.71888.
Nonmuscle myosin II (NM II) is an integral part of essential cellular processes, including adhesion and migration. Mammalian cells express up to three isoforms termed NM IIA, B, and C. We used U2OS cells to create CRISPR/Cas9-based knockouts of all three isoforms and analyzed the phenotypes on homogenously coated surfaces, in collagen gels, and on micropatterned substrates. In contrast to homogenously coated surfaces, a structured environment supports a cellular phenotype with invaginated actin arcs even in the absence of NM IIA-induced contractility. A quantitative shape analysis of cells on micropatterns combined with a scale-bridging mathematical model reveals that NM IIA is essential to build up cellular tension during initial stages of force generation, while NM IIB is necessary to elastically stabilize NM IIA-generated tension. A dynamic cell stretch/release experiment in a three-dimensional scaffold confirms these conclusions and in addition reveals a novel role for NM IIC, namely the ability to establish tensional homeostasis.
非肌肉肌球蛋白 II（NM II）是许多基本细胞过程的重要组成部分，包括黏附和迁移。哺乳动物细胞表达多达三种同工型，分别称为 NM IIA、B 和 C。我们使用 U2OS 细胞，通过 CRISPR/Cas9 系统构建了三种同工型的敲除细胞系，并在均相涂层表面、胶原凝胶和微图案化底物上分析了这些细胞的表型。与均相涂层表面相反，在结构化环境中，即使不存在 NM IIA 诱导的收缩性，也支持具有凹陷的肌动蛋白弧的细胞表型。在微图案上对细胞进行的定量形状分析结合跨尺度数学模型揭示，NM IIA 对于在力产生的初始阶段建立细胞张力是必需的，而 NM IIB 对于弹性稳定 NM IIA 产生的张力是必需的。在三维支架中的细胞动态拉伸/释放实验证实了这些结论，并进一步揭示了 NM IIC 的一个新作用，即建立张力稳态的能力。
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