Restructuring of Lipid Membranes by an Arginine-Capped Peptide Bolaamphiphile

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Researchers

Research units

  • University of Reading

Abstract

We study the self-assembly of arginine-capped bolaamphiphile peptide RA 3 R (A: alanine, R: arginine) together with its binding to model membranes and its cytotoxicity and antimicrobial activity. Anionic 2-oleoyl-1-palmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt/2-oleoyl-1-palmitoyl-sn-glycero-3-phosphoethanolamine (POPG/POPE) vesicles and zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine/2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC/DOPC) vesicles are used as model membranes to mimic bacterial and mammalian cell membranes, respectively. We show that RA 3 R adopts a polyproline-II collagen-like conformation in water. Binding of RA 3 R to POPG/POPE vesicles induces a strong correlation between the lipid bilayers, driven by RA 3 R/POPG attractive electrostatic interaction together with a shift of the intramolecular POPE zwitterionic interaction toward an attractive electrostatic interaction with the RA 3 R. Populations of RA 3 R/POPG/POPE vesicles comprise different bilayer spacings, d A and d B , controlled by the conformation of the lipid chains corresponding to the L β (gel-like) and L α (liquid-crystal) phases, respectively. Cryo-TEM images reveal the presence of vesicles with no internal structure, compartmentalized thin-wall vesicles, or multilayer vesicles with uncorrelated layers and compartmentalization depending on the RA 3 R/POPG/POPE composition. In contrast, the interaction of RA 3 R with multilamellar POPC/DOPC vesicles leads to the decorrelation of the lipid bilayers. RA 3 R was tolerated by skin fibroblast cells for a concentration up to 0.01 wt %, while 0.25 wt % RA 3 R proved to be an efficient antibacterial agent against Gram-positive bacteria L. monocytogenes. Our results highlight the ability of RA 3 R to distinguish between bacterial and mammalian cells and establish this peptide as a candidate to reduce the proliferation of L. monocytogenes bacteria.

Details

Original languageEnglish
Pages (from-to)1302-1311
Number of pages10
JournalLangmuir
Volume35
Issue number5
Publication statusPublished - 5 Feb 2019
MoE publication typeA1 Journal article-refereed

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