Cell elongation along the division axis, or mitotic elongation, mediates proper segregation of chromosomes and other intracellular materials, and is required for completion of cell division. In three‐dimensionally confining extracellular matrices, such as dense collagen gels, dividing cells must generate space to allow mitotic elongation to occur. In principle, cells can generate space for mitotic elongation during cell spreading, prior to mitosis, or via extracellular force generation or matrix degradation during mitosis. However, the processes by which cells drive mitotic elongation in collagen‐rich extracellular matrices remains unclear. Here, it is shown that single cancer cells generate substantial pushing forces on the surrounding collagen extracellular matrix to drive cell division in confining collagen gels and allow mitotic elongation to proceed. Neither cell spreading, prior to mitosis, nor matrix degradation, during spreading or mitotic elongation, are found to be required for mitotic elongation. Mechanistically, laser ablation studies, pharmacological inhibition studies, and computational modeling establish that pushing forces generated during mitosis in collagen gels arise from a combination of interpolar spindle elongation and cytokinetic ring contraction. These results reveal a fundamental mechanism mediating cell division in confining extracellular matrices, providing insight into how tumor cells are able to proliferate in dense collagen‐rich tissues.

中文翻译：

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有丝分裂过程中的细胞推动力驱动胶原凝胶中的有丝分裂伸长

细胞沿分裂轴的伸长，或有丝分裂伸长，介导染色体和其他细胞内物质的适当分离，并且是完成细胞分裂所必需的。在三维限制的细胞外基质中，例如致密的胶原凝胶，分裂细胞必须产生空间以允许有丝分裂伸长发生。原则上，细胞可以在细胞扩散期间、有丝分裂之前，或通过有丝分裂期间的细胞外力产生或基质降解，产生有丝分裂伸长的空间。然而，细胞在富含胶原蛋白的细胞外基质中驱动有丝分裂伸长的过程仍不清楚。在这里，研究表明，单个癌细胞对周围的胶原细胞外基质产生巨大的推力，以驱动限制胶原凝胶的细胞分裂，并允许有丝分裂伸长进行。发现有丝分裂之前的细胞铺展以及铺展或有丝分裂伸长过程中的基质降解都不是有丝分裂伸长所必需的。从机制上讲，激光消融研究、药理学抑制研究和计算模型证实，胶原凝胶有丝分裂过程中产生的推力是由极间纺锤体伸长和细胞因子环收缩的组合产生的。这些结果揭示了限制细胞外基质中介导细胞分裂的基本机制，为肿瘤细胞如何能够在富含胶原蛋白的致密组织中增殖提供了见解。