Tallman James F, Kambar Nurila, Leal Cecília, Statt Antonia
Department of Materials Science and Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Macromolecules. 2024 Dec 24;57(24):11688-11696. doi: 10.1021/acs.macromol.4c01874. Epub 2024 Nov 28.
There is a long-term interest in creating artificial biomimetic membranes where self-assembled phospholipid bilayers are selectively permeabilized by synthetic channel-like molecules. One example is the coassembly of amphiphilic block copolymers with phospholipids into a hybrid membrane. Hybrid phospholipid block copolymer bilayers display many properties, seen in biomembranes such as selective transport phenomena, synergistic elastic properties, and structural phase transformations. Just like in biomembranes, these fundamental properties of hybrid bilayers are often regulated by lateral phase separation. Understanding the molecular and physical cues that determine the formation of rafts or domains in hybrid membranes, their size, and morphology is paramount to elucidating and programming their function. Employing a combination of coarse-grained molecular dynamics simulations and high-resolution cryogenic electron microscopy, we discovered that phosphatidylcholine-cholesterol bilayers hybridized with poly(butadiene--ethylene oxide) develop two distinct phase-separated morphologies. At molar fractions of polymer above 10 mol % the expected molecular distribution into lipid-rich and polymer-rich domains is observed. However, at low polymer content, a new structure develops in which the bilayer leaflets unzip (but remain continuous) to incorporate nanodomains of hydrophobic butadiene globules. We conjecture that unzipping is energetically more favorable than sustaining the hydrophobic mismatch between butadiene blocks and phospholipid acyl chains. These findings offer new insights into the morphology of biomembranes upon the insertion of transmembrane proteins with bulky hydrophobic residues.
长期以来,人们一直对创建人工仿生膜感兴趣,在这种膜中,自组装的磷脂双层被合成的通道样分子选择性地渗透。一个例子是两亲性嵌段共聚物与磷脂共组装成混合膜。混合磷脂嵌段共聚物双层具有许多在生物膜中可见的特性,如选择性运输现象、协同弹性特性和结构相变。就像在生物膜中一样,这些混合双层的基本特性通常由横向相分离来调节。了解决定混合膜中筏或结构域的形成、其大小和形态的分子和物理线索对于阐明和规划它们的功能至关重要。通过结合粗粒度分子动力学模拟和高分辨率低温电子显微镜,我们发现与聚(丁二烯 - 环氧乙烷)杂交的磷脂酰胆碱 - 胆固醇双层形成了两种不同的相分离形态。在聚合物摩尔分数高于10 mol%时,观察到预期的分子分布到富含脂质和富含聚合物 的结构域中。然而,在低聚合物含量下,会形成一种新结构,其中双层小叶会拉开(但保持连续)以纳入疏水丁二烯小球的纳米域。我们推测,拉开比维持丁二烯嵌段与磷脂酰基链之间的疏水错配在能量上更有利。这些发现为插入具有大量疏水残基的跨膜蛋白后生物膜的形态提供了新的见解。
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