Styrene-maleic acid copolymers form SMALPs by pulling lipid patches out from the lipid bilayerстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 26 апреля 2019 г.
Аннотация:Amphiphilic copolymers composed of alternating maleic acid and styrene (SMA) monomers caused a major methodical breakthrough in the study of membrane proteins. They were found to directly release phospholipids and membrane proteins both from artificial and natural bilayers yielding stable water-soluble discoidal SMA/lipid particles (SMALPs) of uniform size. Although many empirical studies indicate the great potency of SMALPs for membrane protein research, the mechanisms of their formation remain obscure. It is unknown which factors account for the very assembly of SMALPs and govern their uniform size. We have developed a coarse-grained (CG) molecular model of SMA copolymers based on the MARTINI CG force field and used it to probe the behavior of SMA copolymers with varying composition/charge/concentration in solution as well as their interaction with lipid membranes. First, we found that SMA copolymers tend to aggregate in solution into clusters, which could account for the uniform size of SMALPs. Next, MD simulations showed that SMA copolymers with styrene:maleic acid ratios of 2:1 and 3:1 differently interacted with lipid bilayer. While clusters of 2:1 SMA copolymers induced membrane poration, the clusters of 3:1 SMA copolymers extracted lipid patches from the membrane yielding SMALP-like structures. Analysis of MD simulation trajectories and comparison with experimental data indicate that the formation of SMALPs is due to the interactions of three-styrene blocks with hydrophobic lipid moieties.