Bulging and budding of lipid droplets from symmetric and asymmetric membranes: competition between membrane elastic energy and interfacial energy
Bulging and budding of lipid droplets from symmetric and asymmetric membranes: competition between membrane elastic energy and interfacial energy
复制标题
对称和非对称膜脂滴的膨胀和出芽：膜弹性能和界面能之间的竞争
作者：
Wang Meng;Yi Xin
脂滴是细胞内普遍存在的细胞器，调节中性脂质的储存和水解，并在细胞代谢和其他功能如蛋白质运输和与免疫反应协调中发挥关键作用。虽然脂滴在真核生物中被广泛观察到，但尚不清楚中性脂质和脂质膜之间的机械相互作用如何以及哪些方面有助于初生脂滴从内质网中凸出和出芽，特别是膜不对称性和自发曲率对脂滴形成的影响在理论上没有合理化。在这里，我们进行了全面的理论研究的力学行为嵌入在两个脂质单分子层之间的相同或不同的机械性能，并指出膜的弯曲刚度，张力和自发曲率，脂滴的大小，和中性脂质和覆盖的脂质小叶之间的界面能共同发挥关键作用，在调节的生长和出芽转变的脂滴。结果发现，嵌入超过临界体积的中性脂质可以经历一个不连续的形状转变，从一个透镜状配置的出芽状态与球形凸起配置。此外，一个积极的脂质单层自发曲率和较小的单层弯曲刚度和张力促进出芽过渡。萌芽相图占这些特征的相互作用状态的建立。基于小变形下的膜理论和球的假设，我们得到了凸起轮廓的解析解，它可以用来估计界面能的值。我们的研究结果揭示了脂滴形成和出芽的基本机制，并且对回声脂质体稳定性和纳米颗粒的细胞掺入的研究具有广泛的意义。
Lipid droplets are ubiquitous intracellular organelles regulating the storage and hydrolysis of neutral lipids, and play key roles in cellular metabolism and other functions such as protein trafficking and coordinating with immune responses. Though lipid droplets are widely observed in eukaryotic organisms, it remains unclear how and what aspects of mechanical interaction between the neutral lipids and lipid membranes contribute to the bulging and budding of nascent lipid droplets from the endoplasmic reticulum, and particularly effects of membrane asymmetry and spontaneous curvature on lipid droplet formation are not theoretically rationalized. Here we conduct a comprehensive theoretical study on the mechanical behaviors of lipid droplets embedded in between two lipid monolayers of the same or different mechanical properties, and indicate that the membrane bending rigidity, tension and spontaneous curvature, lipid droplet size, and interfacial energy between the neutral lipids and covering lipid leaflets collectively play key roles in regulating the growth and budding transition of lipid droplets. It is found that the embedded neutral lipids beyond a critical volume could undergo a discontinuous shape transition from a lens-like configuration to a budding state with a spherical bulge configuration. Moreover, a positive lipid monolayer spontaneous curvature and smaller monolayer bending rigidity and tension facilitate the budding transition. Budding phase diagrams accounting for these characteristic interaction states are established. Based on the membrane theory at small deformation before budding and the assumption of spherical configuration after budding, we obtain analytical solutions on the bulge profiles, which can be used to estimate the value of interfacial energy. Our results uncover the fundamental mechanics of the lipid droplet formation and budding, and are of broad interest to the studies of echogenic liposome stability and cellular incorporation of nanoparticles.