纤维介导细胞极化的能量约束
Energetic constraints on filament mediated cell polarization
摘要：
细胞极化是许多细胞过程的基础，例如分化、迁移和萌芽。许多活细胞，如芽殖酵母和裂殖酵母，使用细胞骨架结构主动将蛋白质运输到膜上的一个位置，并产生高密度的膜结合蛋白质点。然而，热力学约束基于质子的细胞极化仍然未知。我们通过数学建模表明，细胞极化需要细致平衡被打破，我们量化的自由能成本保持极化状态的细胞。我们的研究表明，细致平衡不仅可以通过蛋白质沿着细丝的主动运输来打破，而且还可以通过化学修饰循环来打破，从而允许细致平衡通过蛋白质在细丝、膜和胞质溶胶之间的穿梭来打破。因此，我们的模型表明，细胞极化可以建立通过两个不同的驱动机制，一个基于主动运输和非平衡结合的基础上。此外，该模型预测，驱动绑定过程比基于运输的过程消耗的自由能少几个数量级，以创建相同的膜点。沿着细丝的主动运输可能足以产生膜结合蛋白的极化分布，但是蛋白质本身的额外化学修饰循环对运输细丝上的蛋白质的物理排斥更有效且不太敏感，从而提供了对裂殖酵母中的Pom 1/Tea 1/Tea 4系统和芽殖酵母中的Cdc 42系统的设计原理的深入了解。
英文摘要：
Cell polarization underlies many cellular processes, such as differentiation, migration, and budding. Many living cells, such as budding yeast and fission yeast, use cytoskeletal structures to actively transport proteins to one location on the membrane and create a high density spot of membrane-bound proteins. Yet, the thermodynamic constraints on filament-based cell polarization remain unknown. We show by mathematical modeling that cell polarization requires detailed balance to be broken, and we quantify the free-energy cost of maintaining a polarized state of the cell. Our study reveals that detailed balance cannot only be broken via the active transport of proteins along filaments, but also via a chemical modification cycle, allowing detailed balance to be broken by the shuttling of proteins between the filament, membrane, and cytosol. Our model thus shows that cell polarization can be established via two distinct driving mechanisms, one based on active transport and one based on non-equilibrium binding. Furthermore, the model predicts that the driven binding process dissipates orders of magnitude less free-energy than the transport-based process to create the same membrane spot. Active transport along filaments may be sufficient to create a polarized distribution of membrane-bound proteins, but an additional chemical modification cycle of the proteins themselves is more efficient and less sensitive to the physical exclusion of proteins on the transporting filaments, providing insight in the design principles of the Pom1/Tea1/Tea4 system in fission yeast and the Cdc42 system in budding yeast.
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