Dolgitzer David, Plaza-Rodríguez Alma I, Iglesias Miguel A, Jacob Mark Allan C, Todd Bethany A, Robinson Douglas N, Iglesias Pablo A
Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, Maryland.
Oncology-Quantitative Sciences Department, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Biophys J. 2025 Jan 7;124(1):62-76. doi: 10.1016/j.bpj.2024.10.020. Epub 2024 Nov 8.
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.
细胞感知和响应机械力的能力对于其在周围环境中移动以及与相邻细胞相互作用至关重要。肌球蛋白II和皮层肌动蛋白I在细胞质中形成称为收缩工具包(CKs)的复合物,通过在施加应力的部位局部积累来促进细胞骨架反应。在这里,我们提出了一个关于盘基网柄菌机械响应性的计算模型,基于实验测量参数分析CKs在机械响应机制中的作用。我们的模型进一步阐述了在施加机械力前后收缩蛋白的既定分布和通道化。通过比较野生型细胞、缺失突变体、过表达突变体以及CK形成缺陷细胞对机械应力的反应,我们严格验证了我们的计算结果。在体内测量平衡状态下肌球蛋白II皮质分布的平行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,并为机械响应性的调节动力学提供了新的见解。