Mohan Krithika, Luo Tianzhi, Robinson Douglas N, Iglesias Pablo A
Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
J R Soc Interface. 2015 Aug 6;12(109):20150512. doi: 10.1098/rsif.2015.0512.
Cells undergo controlled changes in morphology in response to intracellular and extracellular signals. These changes require a means for sensing and interpreting the signalling cues, for generating the forces that act on the cell's physical material, and a control system to regulate this process. Experiments on Dictyostelium amoebae have shown that force-generating proteins can localize in response to external mechanical perturbations. This mechanosensing, and the ensuing mechanical feedback, plays an important role in minimizing the effect of mechanical disturbances in the course of changes in cell shape, especially during cell division, and likely in other contexts, such as during three-dimensional migration. Owing to the complexity of the feedback system, which couples mechanical and biochemical signals involved in shape regulation, theoretical approaches can guide further investigation by providing insights that are difficult to decipher experimentally. Here, we present a computational model that explains the different mechanosensory and mechanoresponsive behaviours observed in Dictyostelium cells. The model features a multiscale description of myosin II bipolar thick filament assembly that includes cooperative and force-dependent myosin-actin binding, and identifies the feedback mechanisms hidden in the observed mechanoresponsive behaviours of Dictyostelium cells during micropipette aspiration experiments. These feedbacks provide a mechanistic explanation of cellular retraction and hence cell shape regulation.
细胞会根据细胞内和细胞外信号经历形态上的可控变化。这些变化需要一种手段来感知和解读信号线索，产生作用于细胞物质的力，以及一个控制系统来调节这一过程。对盘基网柄菌变形虫的实验表明，产生力的蛋白质可以响应外部机械扰动而定位。这种机械传感以及随之而来的机械反馈，在最小化细胞形状变化过程中，特别是细胞分裂期间，以及可能在其他情况下，如三维迁移过程中机械干扰的影响方面发挥着重要作用。由于耦合了形状调节中涉及的机械和生化信号的反馈系统很复杂，理论方法可以通过提供难以通过实验解读的见解来指导进一步的研究。在这里，我们提出了一个计算模型，该模型解释了在盘基网柄菌细胞中观察到的不同机械传感和机械响应行为。该模型具有对肌球蛋白II双极粗丝组装的多尺度描述，包括协同和力依赖性的肌球蛋白 - 肌动蛋白结合，并识别了在微量移液器抽吸实验中盘基网柄菌细胞观察到的机械响应行为中隐藏的反馈机制。这些反馈为细胞收缩以及因此的细胞形状调节提供了一个机械学解释。
