Indexed on: 31 Jul '18Published on: 31 Jul '18Published in: Langmuir
Here we study the self-assembly of arginine capped bolaamphiphile peptide RA3R (A: alanine, R: arginine) together with its binding to model membranes and RA3R cytotoxic and antimicrobial activities. 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 RA3R adopts a polyproline II collagen-like conformation in water. Binding of RA3R to POPG/POPE vesicles induces a strong correlation between the lipid bilayers, driven by RA3R/POPG attractive electrostatic interaction together with a shift of the intramolecular POPE zwitterionic interaction towards an attractive electrostatic interaction with the RA3R. Populations of RA3R/POPG/POPE vesicles comprise different bilayer spacings dA and dB, controlled by the conformation of the lipid chains corresponding to the Lβ (gel-like) and Lα (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 RA3R/POPG/POPE composition. In contrast, the interaction of RA3R with multilamellar POPC/DOPC vesicles leads to the de-correlation of the lipid bilayers. RA3R was tolerated by skin fibroblast cells for a concentration up to 0.01wt%, while 0.25 wt% RA3R probed to be an efficient antibacterial agent against Gram-positive bacteria L. monocytogenes. Our results highlight the ability of RA3R to distinguish between bacterial and mammalian cells and set this peptide as a candidate to reduce proliferation of L. monocytogenes bacteria.