Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28403, United States.
Langmuir. 2023 Aug 1;39(30):10289-10300. doi: 10.1021/acs.langmuir.3c00538. Epub 2023 Jul 21.
Lipid bilayer membranes are often represented as a continuous nonpolar slab with a certain thickness bounded by two more polar interfaces. Phenomena such as peptide binding to the membrane surface, folding, insertion, translocation, and diffusion are typically interpreted on the basis of this view. In this Perspective, I argue that this membrane representation as a hydrophobic continuum solvent is not adequate to understand peptide-lipid interactions. Lipids are not small compared to membrane-active peptides: their sizes are similar. Therefore, peptide diffusion needs to be understood in terms of free volume, not classical continuum mechanics; peptide solubility or partitioning in membranes cannot be interpreted in terms of hydrophobic mismatch between membrane thickness and peptide length; peptide folding and translocation, often involving cationic peptides, can only be understood if realizing that lipids adapt to the presence of peptides and the membrane may undergo considerable lipid redistribution in the process. In all of those instances, the detailed molecular interactions between the peptide residues and the lipid components are essential to understand the mechanisms involved.
脂质双层膜通常被表示为一个具有一定厚度的连续非极性片，由两个更极性的界面所限定。肽与膜表面的结合、折叠、插入、易位和扩散等现象通常都是基于这种观点来解释的。在本文观点中，我认为这种将膜表示为疏水连续溶剂的方法并不足以理解肽-脂相互作用。与膜活性肽相比，脂质并不小：它们的大小相似。因此，肽的扩散需要根据自由体积来理解，而不是经典的连续力学；肽在膜中的溶解度或分配不能用膜厚度和肽长度之间的疏水失配来解释；涉及阳离子肽的肽折叠和易位，只有意识到脂质会适应肽的存在，并且在这个过程中膜可能会发生相当大的脂质重分布，才能被理解。在所有这些情况下，肽残基与脂质成分之间的详细分子相互作用对于理解所涉及的机制是至关重要的。
