MEMPHYS: Center for Biomembrane Physics, University of Southern Denmark, Campusvej 55, Odense 5230 M, Denmark.
MEMPHYS: Center for Biomembrane Physics, University of Southern Denmark, Campusvej 55, Odense 5230 M, Denmark.
Chem Phys Lipids. 2018 Mar;211:93-99. doi: 10.1016/j.chemphyslip.2017.11.010. Epub 2017 Nov 21.
We address unresolved questions of the energetics and mechanism of lipid droplet (LD) biogenesis, and of the role of caveolins in the endoplasmic reticulum (ER) and in mature LDs. LDs are eukaryotic repositories of neutral lipids, which are believed to be synthesised in the ER. We investigate the effects of a curvature-inducing protein, caveolin-1, on the formation and structure of a spontaneously aggregated triolein (TO) lipid lens in a flat lipid bilayer using molecular dynamics (MD) simulations. A truncated form of caveolin-1 (Cav1) localises on the interface between the spontaneously formed TO aggregate and the bulk bilayer, and thins the bilayer at the edge of the aggregate, which may contribute to lowering the energy barrier for pinching off the aggregate from the host bilayer. Simulations of fully mature LDs do not conclusively establish the optimal localisation of Cav1 in LDs, but when Cav1 is in the LD core, the distribution of both neutral lipids in the LD core, and of phospholipids on the engulfing monolayer are altered significantly. Our simulations provide an unprecedented molecular description of the distribution and dynamics of various lipid species in both mature LDs and in the nascent LD inside the bilayer.
我们解决了关于脂滴 (LD) 生物发生的能量学和机制以及 caveolins 在内质网 (ER) 和成熟 LD 中的作用的未解决问题。LD 是真核细胞中性脂质的储存库，据信这些脂质是在 ER 中合成的。我们使用分子动力学 (MD) 模拟研究了曲率诱导蛋白 caveolin-1 对在平坦脂质双层中自发聚集的三油酸甘油酯 (TO) 脂质透镜的形成和结构的影响。caveolin-1 的截断形式 (Cav1) 定位于自发形成的 TO 聚集体与主体双层之间的界面上，并在聚集体的边缘使双层变薄，这可能有助于降低从主体双层上剥离聚集体的能量势垒。对完全成熟的 LD 的模拟并不能明确确定 Cav1 在 LD 中的最佳定位，但当 Cav1 在 LD 核心中时，LD 核心中的中性脂质以及吞噬单层上的磷脂的分布都会发生显著改变。我们的模拟为成熟 LD 以及双层内新生 LD 中各种脂质物种的分布和动力学提供了前所未有的分子描述。
