Modulating charge-dependent and folding-mediated antimicrobial interactions at peptide-lipid interfaces.
Peptide-lipid interactions support a variety of biological functions. Of particular interest are those that underpin fundamental mechanisms of innate immunity that are programmed in host defense or antimicrobial peptide sequences found virtually in all multicellular organisms. Here we synthetically modulate antimicrobial peptide-lipid interactions using an archetypal helical antimicrobial peptide and synthetic membranes mimicking bacterial and mammalian membranes in solution. We probe these interactions as a function of membrane-induced folding, membrane stability and peptide-lipid ratios using a correlative approach encompassing light scattering and spectroscopy measurements such as circular dichroism spectroscopy, fluorescence and nuclear magnetic resonance spectroscopy. The peptide behavior is assessed against that of its anionic counterpart having similar propensities for α-helical folding. The results indicate strong correlations between peptide folding and membrane type, supporting folding-responsive binding of antimicrobial peptides to bacterial membranes. The study provides a straightforward approach for modulating structure-activity relationships in the context of membrane-induced antimicrobial action, thus holding promise for the rational design of potent antimicrobial agents.
European Commission, DG Joint Research Centre, Via Enrico Fermi, 2749, Ispra, VA, 21027, Italy.
Patrizia
P
Iavicoli
European Commission, DG Joint Research Centre, Via Enrico Fermi, 2749, Ispra, VA, 21027, Italy.
François
F
Rossi
National Physical Laboratory, Teddington, TW11 0LW, UK.
Baptiste
B
Lamarre
National Physical Laboratory, Teddington, TW11 0LW, UK.
Angelo
A
Bella
National Physical Laboratory, Teddington, TW11 0LW, UK.
Maxim G
MG
Ryadnov
European Commission, DG Joint Research Centre, Via Enrico Fermi, 2749, Ispra, VA, 21027, Italy. luigi.calzolai@ec.europa.eu.
Luigi
http://orcid.org/0000-0002-8474-7974
L
Calzolai
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D053835:Unilamellar Liposomes / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D053835:Unilamellar Liposomes
Antimicrobial peptides; Circular dichroism; Dynamic light scattering; Fluorescence; Nuclear magnetic resonance; Synthetic membranes