Centro de Ciências Naturais e Humanas , Universidade Federal do ABC , Avenida dos Estados 5001 , CEP 09210-580 Santo André , SP , Brazil.
J Phys Chem B. 2018 Jul 12;122(27):6954-6965. doi: 10.1021/acs.jpcb.8b03406. Epub 2018 May 30.
Phase-separated membrane domains, also known as lipid rafts, are believed to play an important role in cell function. Although most rafts are sterol-enriched membrane regions, evidence suggests that living cells may also contain gel-like rafts. Interactions between gel and fluid domains have a large impact on membrane properties, as is the case with permeability. The membrane permeability may reach a peak at the main phase transition temperature, by far exceeding the values recorded at the fluid phase. It has been proposed that gel-fluid interfaces are leaky, but the effect has not yet been demonstrated at the molecular level. Here, we performed atomistic molecular dynamics simulations of phospholipid bilayers with coexisting gel-like and fluid domains. We found that the thickness mismatch between both phases, the membrane elasticity, and the lipid packing acted together to promote the formation of a thickness minimum at the gel-fluid interface. Free energy calculations showed that pore-mediated ionic permeation was strongly facilitated at the constriction region, whereas water permeation by simple diffusion was only marginally affected. Long-lived, peristaltic undulations were recorded at the bulk fluid phase near the main transition temperature. They gave rise to thickness minima that, although shallower than the interface constrictions, could also enhance permeability. Finally, we demonstrated that an interface constriction was also formed at the boundaries of regular, cholesterol-enriched lipid rafts. Our simulation results will hopefully contribute to a better understanding of biological processes such as transport, signaling, and cellular damage promoted by low temperature and dehydration.
相分离的膜域，也称为脂筏，被认为在细胞功能中发挥重要作用。尽管大多数筏都是富含固醇的膜区域，但有证据表明，活细胞中可能还存在凝胶状的筏。凝胶和流体域之间的相互作用对膜性质有很大影响，例如渗透性。膜的渗透性在主相转变温度时可能达到峰值，远远超过在流体相时记录的值。有人提出凝胶-流体界面是有渗漏的，但这一效应尚未在分子水平上得到证明。在这里，我们对具有共存凝胶状和流体域的磷脂双层膜进行了原子分子动力学模拟。我们发现，两个相之间的厚度不匹配、膜弹性和脂质堆积共同作用，促进了在凝胶-流体界面处形成厚度最小值。自由能计算表明，在收缩区，孔介导的离子渗透得到了强烈促进，而单纯扩散的水渗透则只有轻微影响。在主转变温度附近的体相流体中记录到长寿命的蠕动波。它们产生了厚度最小值，尽管比界面收缩区浅，但也可以增强渗透性。最后，我们证明在常规富含胆固醇的脂筏的边界处也形成了界面收缩区。我们的模拟结果有望有助于更好地理解低温和脱水促进的运输、信号传递和细胞损伤等生物学过程。
