School of Mathematics and Statistics, University of South Australia, Mawson Lakes, SA 5095, Australia.
J Theor Biol. 2010 Jun 7;264(3):952-61. doi: 10.1016/j.jtbi.2010.02.025. Epub 2010 Feb 23.
The biogenesis of lipid droplets (LD) in the yeast Saccharomyces cerevisiae was theoretically investigated on basis of a biophysical model. In accordance with the prevailing model of LD formation, we assumed that neutral lipids oil-out between the membrane leaflets of the endoplasmic reticulum (ER), resulting in LD that bud-off when a critical size is reached. Mathematically, LD were modeled as spherical protuberances in an otherwise planar ER membrane. We estimated the local phospholipid composition, and calculated the change in elastic free energy of the membrane caused by nascent LD. Based on this model calculation, we found a gradual demixing of lipids in the membrane leaflet that goes along with an increase in surface curvature at the site of LD formation. During demixing, the phospholipid monolayer was able to gain energy during LD growth, which suggested that the formation of curved interfaces was supported by or even driven by lipid demixing. In addition, we show that demixing is thermodynamically necessary as LD cannot bud-off otherwise. In the case of Saccharomyces cerevisiae our model predicts a LD bud-off diameter of about 12 nm. This diameter is far below the experimentally determined size of typical yeast LD. Thus, we concluded that if the standard model of LD formation is valid, LD biogenesis is a two step process. Small LD are produced from the ER, which subsequently ripe within the cytosol through a series of fusions.
酵母细胞内脂滴（LD）的生物发生过程是基于生物物理模型进行理论研究的。根据 LD 形成的流行模型，我们假设中性脂质在内质网（ER）的膜小叶之间油出，导致当达到临界尺寸时 LD 出芽。从数学上讲，LD 被建模为在其他平面 ER 膜中的球形突起。我们估计了局部磷脂组成，并计算了由新生 LD 引起的膜弹性自由能的变化。基于该模型计算，我们发现膜小叶中的脂质逐渐分相，同时在 LD 形成部位的表面曲率增加。在分相过程中，磷脂单层在 LD 生长过程中能够获得能量，这表明弯曲界面的形成得到了脂质分相的支持，甚至是由其驱动的。此外，我们还表明，分相在热力学上是必要的，否则 LD 就无法出芽。对于酿酒酵母，我们的模型预测 LD 的出芽直径约为 12nm。这个直径远远低于实验测定的典型酵母 LD 的尺寸。因此，我们得出结论，如果 LD 形成的标准模型是有效的，那么 LD 的生物发生是一个两步过程。从小的 ER 中产生 LD，随后通过一系列融合在细胞质中成熟。
