Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, Rome, Italy.
Department of Basic and Applied Sciences for Engineering, Sapienza University of Rome, Rome, Italy.
Sci Rep. 2024 Jun 18;14(1):14003. doi: 10.1038/s41598-024-64685-2.
Mesoscale physics bridges the gap between the microscopic degrees of freedom of a system and its large-scale continuous behavior and highlights the role of a few key quantities in complex and multiscale phenomena, like dynamin-driven fission of lipid membranes. The dynamin protein wraps the neck formed during clathrin-mediated endocytosis, for instance, and constricts it until severing occurs. Although ubiquitous and fundamental for life, the cooperation between the GTP-consuming conformational changes within the protein and the full-scale response of the underlying lipid substrate is yet to be unraveled. In this work, we build an effective mesoscopic model from constriction to fission of lipid tubules based on continuum membrane elasticity and implicitly accounting for ratchet-like power strokes of dynamins. Localization of the fission event, the overall geometry, and the energy expenditure we predict comply with the major experimental findings. This bolsters the idea that a continuous picture emerges soon enough to relate dynamin polymerization length and membrane rigidity and tension with the optimal pathway to fission. We therefore suggest that dynamins found in in vivo processes may optimize their structure accordingly. Ultimately, we shed light on real-time conductance measurements available in literature and predict the fission time dependency on elastic parameters.
介观物理学弥合了系统微观自由度与其大尺度连续行为之间的差距,并强调了少数关键量在复杂和多尺度现象中的作用,如网格蛋白介导的内吞作用中脂质膜的动力蛋白驱动裂变。例如,动力蛋白蛋白包裹在网格蛋白介导的内吞作用过程中形成的颈部,并使其收缩,直到发生断裂。尽管普遍存在且对生命至关重要,但蛋白质内的 GTP 消耗构象变化与基础脂质底物的全面反应之间的合作尚未被揭示。在这项工作中,我们基于连续膜弹性建立了一个从脂质小管收缩到裂变的有效介观模型,并隐含地考虑了动力蛋白的棘轮式功率冲程。我们预测的裂变事件的定位、整体几何形状和能量消耗与主要的实验结果相符。这支持了这样一种观点,即一个连续的图景很快就会出现,将动力蛋白聚合长度和膜刚性与张力与裂变的最佳途径联系起来。因此,我们认为在体内过程中发现的动力蛋白可能会相应地优化其结构。最终,我们阐明了文献中可用的实时电导测量,并预测了弹性参数对裂变时间的依赖性。