Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
J Chem Phys. 2024 Sep 21;161(11). doi: 10.1063/5.0230727.
Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane.
脂质筏是鞘脂、胆固醇和特定膜蛋白的纳米级组装体。它们被认为是真核质膜实验观察到的侧向异质性的基础，并与许多细胞过程有关，如信号转导和运输。由饱和脂质、不饱和脂质和胆固醇组成的三元模型膜是常见的替代品，因为它们在有序（lo）相和无序（ld）相之间存在相共存，并有一个相关的临界点。然而，质膜在脂质类型、脂质丰度、叶层张力和相应的胆固醇分布方面也是不对称的，这表明筏不能与关于弹性、曲率扭矩和内部机械应力的问题分开研究。不幸的是，很难在一个能够访问足够长的长度和时间尺度的单一模型中捕捉到这广泛的物理现象。在这里，我们扩展了高度粗粒化的 Cooke 脂质模型，该模型在曲率弹性前沿得到了广泛的描述，也可以表示类似筏的 lo/ld 混合热力学。特别是，我们捕捉到了共存区域的形状和连接线，随着胆固醇的加入，该区域变窄，在临界点终止，并且具有共存相，反映了膜有序性和脂质堆积的关键差异。我们还研究了弹性和脂质扩散对于相分离和纯系统的影响，以及胆固醇的加入如何改变它们。我们预计，这个模型将为具有组成上不同的叶层的膜提供重要的见解，这些叶层可能处于不同的压力下，如质膜，从而为 lo/ld 相分离和相关的脂质筏问题提供重要的见解。
