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A continuum model of mechanosensation based on contractility kit assembly
Biophysical Journal ( IF 3.2 ) Pub Date : 2024-11-08 , DOI: 10.1016/j.bpj.2024.10.020
David Dolgitzer, Alma I. Plaza-Rodríguez, Miguel A. Iglesias, Mark Allan Co Jacob, Bethany Todd, Douglas N. Robinson, Pablo A. Iglesias

The ability of cells to sense and respond to mechanical forces is crucial for navigating their environment and interacting with neighboring cells. Myosin II and cortexillin I form complexes known as contractility kits (CKs) in the cytosol, which facilitate a cytoskeletal response by accumulating locally at the site of inflicted stress. Here, we present a computational model for mechanoresponsiveness in Dictyostelium, analyzing the role of CKs within the mechanoresponsive mechanism grounded in experimentally measured parameters. Our model further elaborates on the established distributions and channeling of contractile proteins before and after mechanical force application. We rigorously validate our computational findings by comparing the responses of wild-type cells, null mutants, overexpression mutants, and cells deficient in CK formation to mechanical stresses. Parallel in vivo experiments measuring myosin II cortical distributions at equilibrium provide additional validation. Our results highlight the essential functions of CKs in cellular mechanosensitivity and suggest new insights into the regulatory dynamics of mechanoresponsiveness.

中文翻译:


基于收缩性套件组装的机械感觉连续体模型



细胞感知和响应机械力的能力对于导航环境和与邻近细胞相互作用至关重要。肌球蛋白 II 和皮质蛋白 I 在胞质溶胶中形成称为收缩性试剂盒 (CK) 的复合物,它们通过在施加压力的部位局部积累来促进细胞骨架反应。在这里,我们提出了一个 Dictyostelium 机械响应性的计算模型,分析了 CKs 在基于实验测量参数的机械响应机制中的作用。我们的模型进一步详细说明了施加机械力之前和之后收缩蛋白的既定分布和通道。我们通过比较野生型细胞、无效突变体、过表达突变体和 CK 形成缺陷细胞对机械应力的反应,严格验证了我们的计算结果。测量平衡时肌球蛋白 II 皮质分布的平行体内实验提供了额外的验证。我们的结果突出了 CKs 在细胞机械敏感性中的基本功能,并为机械反应性的调节动力学提出了新的见解。
更新日期:2024-11-08
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