Restructuring of Lipid Membranes by an Arginine-Capped Peptide Bolaamphiphile.
Valeria CastellettoRuth H BarnesKimon-Andreas KaratzasCharlotte J C Edwards-GayleFrancesca GrecoIan William HamleyJani SeitsonenJanne RuokolainenPublished in: Langmuir : the ACS journal of surfaces and colloids (2018)
We study the self-assembly of arginine-capped bolaamphiphile peptide RA3R (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 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 toward 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 decorrelation of the lipid bilayers. RA3R was tolerated by skin fibroblast cells for a concentration up to 0.01 wt %, while 0.25 wt % RA3R proved 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 establish this peptide as a candidate to reduce the proliferation of L. monocytogenes bacteria.
Keyphrases
- rheumatoid arthritis
- disease activity
- ankylosing spondylitis
- molecular dynamics simulations
- interstitial lung disease
- nitric oxide
- systemic lupus erythematosus
- magnetic resonance
- single cell
- stem cells
- mesenchymal stem cells
- fatty acid
- cell death
- magnetic resonance imaging
- induced apoptosis
- high resolution
- oxidative stress
- bone marrow
- anti inflammatory
- multidrug resistant
- pi k akt
- crystal structure
- binding protein
- hyaluronic acid
- dna binding