反向水泡生长模型解释了细胞机械适应过程中的巨泡动力学
Model of inverse bleb growth explains giant vacuole dynamics during cell mechanoadaptation
摘要：
细胞可以通过动态改变其形状来承受表现为大的机械力（例如压力梯度和/或剪切应力）的恶劣环境条件。这样的条件在眼睛的施累姆氏管中实现，其中覆盖内血管壁的内皮细胞经受由房水流出物施加的流体动力学压力梯度。这些细胞在其基底膜上形成充满液体的动态外囊，称为\textit{giant vacuoles}。巨大空泡的反面使人联想到细胞泡，细胞外的细胞质突起由收缩性肌动球蛋白皮质的局部暂时中断触发。反向水泡首次在实验中观察到萌芽血管生成过程中，但其潜在的物理机制知之甚少。在这里，我们确定了巨大的空泡形成为逆起泡，并制定了这个过程的生物物理模型。我们的模型阐明了细胞膜的机械性能如何影响巨大的空泡的形态和动力学，并预测粗化类似于奥斯特瓦尔德成熟之间的多个内陷空泡。我们的研究结果是在定性的协议与观察过程中形成的巨大空泡灌注实验。我们的模型不仅阐明了生物物理机制驱动反向起泡和巨大的空泡动力学，但也确定了细胞响应的压力负荷，是相关的许多实验环境的普遍特征。
英文摘要：
Cells can withstand hostile environmental conditions manifest as large mechanical forces such as pressure gradients and/or shear stresses by dynamically changing their shape. Such conditions are realized in the Schlemm's canal of the eye where endothelial cells that cover the inner vessel wall are subjected to the hydrodynamic pressure gradients exerted by the aqueous humor outflow. These cells form fluid-filled dynamic outpouchings of their basal membrane called \textit{giant vacuoles}. The inverse of giant vacuoles are reminiscent of cellular blebs, extracellular cytoplasmic protrusions triggered by local temporary disruption of the contractile actomyosin cortex. Inverse blebbing has been first observed experimentally during sprouting angiogenesis, but its underlying physical mechanisms are poorly understood. Here, we identify giant vacuole formation as inverse blebbing and formulate a biophysical model of this process. Our model elucidates how cell membrane mechanical properties affect the morphology and dynamics of giant vacuoles and predicts coarsening akin to Ostwald ripening between multiple invaginating vacuoles. Our results are in qualitative agreement with observations from the formation of giant vacuoles during perfusion experiments. Our model not only elucidates the biophysical mechanisms driving inverse blebbing and giant vacuole dynamics, but also identifies universal features of the cellular response to pressure loads that are relevant to many experimental contexts.
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