Raft domains of variable properties and compositions in plasma membrane vesicles
Raft domains of variable properties and compositions in plasma membrane vesicles
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DOI：
10.1073/pnas.1105996108
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发表时间：
2011-07-12
影响因子：
11.1
通讯作者：
Simons, Kai
中科院分区：
文献类型：
--
作者：
Levental, Ilya;Grzybek, Michal;Simons, Kai
生物膜通过各种特定的蛋白质-蛋白质、蛋白质-脂质和脂质-脂质相互作用来划分功能多样性。其中一个子集是固醇、鞘脂和饱和脂肪脂尾之间的优先相互作用，这些相互作用负责真核膜中液-液结构域的共存，从而产生动态的纳米级组装，其结合受到特定生化信号的调节。最近在分离的质膜（巨大的质膜囊泡和质膜球）中观察到的微观相分离(i)证实了组成复杂膜的相分离能力，（ii）反映了活细胞膜的纳米级组织，（iii）为研究相的组成和性质提供了一个通用的平台。在这里，我们证明了巨质膜囊泡中共存相的性质取决于分离条件，即用于诱导膜起泡的化学物质。我们观察到共存相的相对组成和顺序及其产生的混相之间有很强的相关性。化学未受扰动的质膜反映了这些特性，并验证了化学诱导囊泡的观察结果。最重要的是，我们观察到由相对较小的隔离条件差异引起的具有不同稳定性，顺序和组成的连续体的域。这些结果表明，基于筏脂优先结合的原理，在膜环境中可以产生各种性质的结构域，其复杂性反映了生物膜的复杂性。
Biological membranes are compartmentalized for functional diversity by a variety of specific protein-protein, protein-lipid, and lipid-lipid interactions. A subset of these are the preferential interactions between sterols, sphingolipids, and saturated aliphatic lipid tails responsible for liquid-liquid domain coexistence in eukaryotic membranes, which give rise to dynamic, nanoscopic assemblies whose coalescence is regulated by specific biochemical cues. Microscopic phase separation recently observed in isolated plasma membranes (giant plasma membrane vesicles and plasma membrane spheres) (i) confirms the capacity of compositionally complex membranes to phase separate, (ii) reflects the nanoscopic organization of live cell membranes, and (iii) provides a versatile platform for the investigation of the compositions and properties of the phases. Here, we show that the properties of coexisting phases in giant plasma membrane vesicles are dependent on isolation conditions-namely, the chemicals used to induce membrane blebbing. We observe strong correlations between the relative compositions and orders of the coexisting phases, and their resulting miscibility. Chemically unperturbed plasma membranes reflect these properties and validate the observations in chemically induced vesicles. Most importantly, we observe domains with a continuum of varying stabilities, orders, and compositions induced by relatively small differences in isolation conditions. These results show that, based on the principle of preferential association of raft lipids, domains of various properties can be produced in a membrane environment whose complexity is reflective of biological membranes.