Department of Physics, Indian Institute of Science-Bangalore, C. V. Raman Road, Bangalore, Karnataka 560012, India.
School of Chemical Sciences, National Institute of Science Education and Research, Bhubaneswar, Khurda, Odisha 752050, India.
Phys Rev E. 2022 Apr;105(4-1):044408. doi: 10.1103/PhysRevE.105.044408.
Biological membrane is a complex self-assembly of lipids, sterols, and proteins organized as a fluid bilayer of two closely stacked lipid leaflets. Differential molecular interactions among its diverse constituents give rise to heterogeneities in the membrane lateral organization. Under certain conditions, heterogeneities in the two leaflets can be spatially synchronized and exist as registered domains across the bilayer. Several contrasting theories behind mechanisms that induce registration of nanoscale domains have been suggested. Following a recent study showing the effect of position of lipid tail unsaturation on domain registration behavior, we decided to develop an analytical theory to elucidate the driving forces that create and maintain domain registry across leaflets. Towards this, we formulated a Hamiltonian for a stacked lattice system where site variables capture the lipid molecular properties such as the position of unsaturation and various other interactions that could drive phase separation and interleaflet coupling. We solve the Hamiltonian using Monte Carlo simulations and create a complete phase diagram that reports the presence or absence of registered domains as a function of various Hamiltonian parameters. We find that the interleaflet coupling should be described as a competing enthalpic contribution due to interaction of lipid tail termini, primarily due to saturated-saturated interactions, and an interleaflet entropic contribution from overlap of unsaturated tail termini. A higher position of unsaturation is seen to provide weaker interleaflet coupling. Thermodynamically stable nanodomains could also be observed for certain points in the parameter space in our bilayer model, which were further verified by carrying out extended Monte Carlo simulations. These persistent noncoalescing registered nanodomains close to the lower end of the accepted nanodomain size range also point towards a possible "nanoscale" emulsion description of lateral heterogeneities in biological membrane leaflets.
生物膜是由脂质、甾醇和蛋白质组成的复杂自组装体，组织为两个紧密堆叠的脂质叶层的流体双层。其多种成分之间的差异分子相互作用导致膜侧向组织的异质性。在某些条件下，两个叶层中的异质性可以在空间上同步存在，并作为双层跨越的注册域存在。已经提出了几种关于诱导纳米级域注册的机制的对比理论。在最近的一项研究表明脂质尾部不饱和的位置对域注册行为的影响后，我们决定开发一种分析理论来阐明在叶层之间产生和维持域注册的驱动力。为此，我们为堆叠晶格系统制定了一个哈密顿量，其中位置变量捕获脂质分子特性，例如不饱和的位置和各种其他可以驱动相分离和叶层间耦合的相互作用。我们使用蒙特卡罗模拟求解哈密顿量，并创建一个完整的相图，该相图报告作为各种哈密顿量参数函数的注册域的存在或不存在。我们发现，叶层间耦合应该描述为由于脂质尾部末端的相互作用（主要是由于饱和-饱和相互作用）而产生的竞争焓贡献，以及不饱和尾部末端重叠的叶层间熵贡献。较高的不饱和位置被认为提供较弱的叶层间耦合。在我们的双层模型中，在参数空间的某些点也可以观察到热力学稳定的纳米域，这通过进行扩展蒙特卡罗模拟进一步得到验证。这些靠近可接受的纳米域尺寸范围下限的持久不聚结的注册纳米域也指向生物膜叶层侧向异质性的可能“纳米级”乳剂描述。
