胆固醇在小单层囊泡中的分布。
Cholesterol Distribution in Small Unilamellar Vesicles.
机构信息
School of Physics, Sun Yat-Sen University, Guangzhou 510275, China.
出版信息
J Phys Chem B. 2022 Sep 22;126(37):7135-7142. doi: 10.1021/acs.jpcb.2c01785. Epub 2022 Sep 8.
The plasma membrane has heterogeneity, where the constituents are not only asymmetrically distributed between the inner leaflet and the outer leaflet but also laterally organized within each leaflet. There is still an ongoing controversy over the cholesterol distribution between the two leaflets, and it is also significant to explore the lateral flow and localization of cholesterol. The unilamellar vesicle is extensively employed as a simplified model of the plasma membrane in research studies. In this work, we study the spontaneous spatial distribution of cholesterol in the small unilamellar vesicles with a single type of phospholipid as the bilayer backbone through coarse-grained molecular dynamics simulations. The results show that in a spherical vesicle under ambient pressure, cholesterol is more abundant in the inner leaflet than in the outer leaflet. As the vesicle is deformed under pressurization, the net lateral flow of cholesterol in the two leaflets is in the exactly opposite directions, finally leading to a distribution strongly associated with the monolayer curvature. One of the possible explanations for our results is from the point of view of curvature elastic energy. Another possibility is from the point of view of stress: according to the correlation between the cholesterol distribution and the tail angles of lipids, it is suggested that the possible governing mechanism for the distribution of cholesterol in a membrane is to alleviate the mismatch of stress between the two leaflets. Additionally, we obtain the effect of cholesterol infiltration on the bending modulus and the spontaneous curvature of the vesicles.
质膜具有不均一性,其组成不仅在内外叶层之间不对称分布,而且在每个叶层内也横向排列。关于两层叶之间胆固醇的分布仍然存在争议,探索胆固醇的横向流动和定位也很重要。单分子层囊泡被广泛用作质膜的简化模型,用于研究工作。在这项工作中,我们通过粗粒度分子动力学模拟研究了具有单一类型磷脂双层骨架的小单分子层囊泡中胆固醇在自发空间中的分布。结果表明,在环境压力下的球形囊泡中,胆固醇在内叶层比在外叶层更丰富。随着囊泡在加压下变形,胆固醇在两个叶层中的净横向流动方向完全相反,最终导致与单层曲率强烈相关的分布。我们结果的一种可能解释是从曲率弹性能量的角度出发。另一种可能性是从应力的角度出发:根据胆固醇分布与脂质尾部角度之间的相关性,建议胆固醇在膜中分布的可能控制机制是减轻两个叶层之间的应力不匹配。此外,我们还获得了胆固醇渗透对囊泡弯曲模量和自发曲率的影响。