The ability of large macromolecules to exhibit nontrivial deviations in colligative properties of their aqueous solutions is well-appreciated in polymer physics. Here, we show that this colligative nonideality subjects giant lipid vesicles containing inert macromolecular crowding agents to osmotic pressure differentials when bathed in small-molecule osmolytes at comparable concentrations. The ensuing influx of water across the semipermeable membrane induces characteristic swell-burst cycles: here, cyclical and damped oscillations in size, tension, and membrane phase separation occur en route to equilibration. Mediated by synchronized formation of transient pores, these cycles orchestrate pulsewise ejection of macromolecules from the vesicular interior reducing the osmotic differential in a stepwise manner. These experimental findings are fully corroborated by a theoretical model derived by explicitly incorporating the contributions of the solution viscosity, solute diffusivity, and the colligative nonideality of the osmotic pressure in a previously reported continuum description. Simulations based on this model account for the differences in the details of the noncolligatively induced swell-burst cycles, including numbers and periods of the repeating cycles, as well as pore lifetimes. Taken together, our observations recapitulate behaviors of vesicles and red blood cells experiencing sudden osmotic shocks due to large (hundreds of osmolars) differences in the concentrations of small molecule osmolytes and link intravesicular macromolecular crowding with membrane remodeling. They further suggest that any tendency for spontaneous overcrowding in single giant vesicles is opposed by osmotic stresses and requires independent specific interactions, such as associative chemical interactions or those between the crowders and the membrane boundary.

中文翻译：

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依数非理想性诱导的含有大分子拥挤剂的巨囊泡的脉动门控

大分子在其水溶液的依数性质中表现出重要偏差的能力在聚合物物理学中得到了很好的认可。在这里，我们表明，当在可比浓度的小分子渗透剂中沐浴时，这种依数非理想性使含有惰性大分子拥挤剂的巨型脂质囊泡受到渗透压差的影响。随之而来的水通过半透膜流入会引起特征性的膨胀-爆裂循环：在这里，尺寸、张力和膜相分离的周期性和阻尼振荡发生在达到平衡的过程中。通过瞬时孔的同步形成介导，这些循环协调大分子从囊泡内部的脉冲喷射，以逐步的方式降低渗透压差。这些实验结果得到了一个理论模型的充分证实，该模型通过在先前报道的连续统描述中明确结合溶液粘度、溶质扩散率和渗透压的依数非理想性的贡献而得出。基于该模型的模拟解释了非依数诱导的膨胀-爆裂循环细节的差异，包括重复循环的数量和周期，以及孔隙寿命。综上所述，我们的观察结果概括了由于小分子渗透剂浓度的巨大（数百个渗透压）差异而经历突然渗透冲击的囊泡和红细胞的行为，并将囊泡内大分子拥挤与膜重塑联系起来。