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.

我们解决了脂滴（LD）生物发生的能量学和机制，以及小窝蛋白在内质网（ER）和成熟LDs中的作用尚未解决的问题。LD是中性脂质的真核贮存库，据信是在ER中合成的。我们调查使用分子动力学（MD）模拟在平面脂质双层中自发聚集的三油精（TO）脂质晶状体的曲率诱导蛋白caveolin-1的形成和结构的影响。Caveolin-1（Cav1）的截短形式位于自发形成的TO聚集体和本体双层之间的界面上，并使该双层在聚集体的边缘变薄，这可能有助于降低将夹杂物从夹层中夹出的能垒。宿主双层。完全成熟的LD的模拟不能最终确定LD中Cav1的最佳定位，但是当Cav1位于LD核心时，LD核心中的中性脂质和吞噬单层磷脂的分布都会发生显着变化。我们的模拟为成熟LD和双层内新生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。