Abstract
Cell membranes are heterogeneous in lipid composition which leads to the phase separation with the formation of nanoscopic liquid-ordered domains, also called rafts. There are multiple cell processes whereby the clustering of these domains into a larger one might be involved, which is responsible for such important processes as signal transduction, polarized sorting, or immune response. Currently, antimicrobial amphipathic peptides are considered promising antimicrobial, antiviral, and anticancer therapeutic agents. Here, within the framework of the classical theory of elasticity adapted for lipid membranes, we investigate how the presence of the peptides in a phase-separated membrane influences the fusion of the domains. We show that the peptides tend to occupy the boundaries of liquid-ordered domains and significantly increase the energy barrier of the domain-domain fusion, which might lead to misregulation of raft clustering and adverse consequences for normal cell processes.
Highlights
Membranes 2021, 11, 797. https://Cell plasma membranes comprise about one hundred types of different lipids [1] and display lateral inhomogeneity resulting from in-plane phase separation [2,3,4,5,6,7,8,9]
There is much evidence of a liquid-ordered (Lo )/liquid-disordered (Ld ) phase separation in model lipid membranes, the lipid composition of which resembles the composition of cell plasma membranes [10,11,12,13,14]
Within the framework of the classical theory of elasticity adapted for lipid membranes, we showed that amphipathic peptides, adsorbed on a lipid bilayer with preexisting phase separation, tend to accumulate at the boundaries of Lo domains [36]
Summary
Cell plasma membranes comprise about one hundred types of different lipids [1] and display lateral inhomogeneity resulting from in-plane phase separation [2,3,4,5,6,7,8,9]. There is much evidence of a liquid-ordered (Lo )/liquid-disordered (Ld ) phase separation in model lipid membranes, the lipid composition of which resembles the composition of cell plasma membranes [10,11,12,13,14]. While in model membranes the macroscopic phase separation is frequently observed, domains in cell membranes are nanoscopic [3,5,6]. The malfunctioning of cholesterol biosynthesis as it occurs in
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