Laboratoire de Physique Statistique, Ecole Normale Supérieure, PSL Research University, Sorbonne Université, UPMC Université Paris 06, Université Paris Diderot, CNRS, Paris, France.
Laboratoire de Physique Statistique, Ecole Normale Supérieure, PSL Research University, Sorbonne Université, UPMC Université Paris 06, Université Paris Diderot, CNRS, Paris, France.
Biophys J. 2018 Feb 6;114(3):631-640. doi: 10.1016/j.bpj.2017.12.014.
Cells store excess energy in the form of neutral lipids that are synthesized and encapsulated within the endoplasmic reticulum intermonolayer space. The lipids next demix to form lipid droplets (LDs), which, surprisingly, bud off mostly toward the cytosol. This directional LD formation is critical to energy metabolism, but its mechanism remains poorly understood. Here, we reconstituted the LD formation topology by embedding artificial LDs into the intermonolayer space of bilayer vesicles. We provide experimental evidence that the droplet behavior in the membrane is recapitulated by the physics of three-phase wetting systems, dictated by the equilibrium of surface tensions. We thereupon determined that slight tension asymmetries between the membrane monolayers regulate the droplet budding side. A differential regulation of lipid or protein composition around a forming LD can generate a monolayer tension asymmetry that will determine the LD budding side. Our results offer, to our knowledge, new insights on how the proteins might regulate LD formation side by generating a monolayer tension asymmetry.
细胞将多余的能量以中性脂的形式储存起来，这些脂类在内质网的层间空间中合成并被包裹。接下来，脂类会发生分离，形成脂滴（LD），令人惊讶的是，LD 主要向细胞质方向出芽。这种定向的 LD 形成对于能量代谢至关重要，但它的机制仍不清楚。在这里，我们通过将人工 LD 嵌入双层囊泡的层间空间来重新构建 LD 形成的拓扑结构。我们提供了实验证据，表明膜中的液滴行为可以通过三相润湿系统的物理原理来再现，这是由表面张力的平衡决定的。因此，我们确定了膜单层之间的轻微张力不对称性调节了液滴出芽的一侧。在形成的 LD 周围的脂质或蛋白质组成的差异调节可以产生单层张力不对称性，这将决定 LD 的出芽侧。我们的结果提供了，据我们所知，关于蛋白质如何通过产生单层张力不对称性来调节 LD 形成侧的新见解。
