Interaction between amphiphilic peptides and phospholipid membranes

Abstract

This brief review aims at providing some illustrative examples on the interaction between amphiphilic peptides and phospholipid membranes, an area of significant current interest.Focusing on antimicrobial peptides, factors affecting peptide-membrane interactions are addressed, including effects of peptide length, charge, hydrophobicity, secondary structure, and topology. Effects of membrane composition are also illustrated, including effects of membrane charge, nature of the polar headgroup, and presence of cholesterol and other sterols. Throughout, novel insights on the importance of peptide adsorption density on membrane stability are emphasized, as is the correlation between peptide adsorption, peptide-induced leakage in model liposome systems, peptide-induced lysis of bacteria, and bacteria killing.

(Lipo)polysaccharide interactions of antimicrobial peptides

“…Electrostatic interactions therefore facilitate peptide binding to anionic bacteria membranes. In addition, presence of hydrophobic residues is important for the ability of many AMPs to disrupt membrane bilayers, particularly at high ionic strength, in the presence of serum, and for low-charged pathogens (6). Key for AMP functionality is membrane selectivity, so that bacteria and other microbes are efficiently killed, while human cells are left intact.…”

“…Several mechanisms have been proposed for AMP-induced membrane disruption, including formation of pore formation and membrane disruption by detergent-like effects (6). For pore formation, the peptide initially adsorbs at the membrane surface, where it subsequently inserts and induces a positive curvature strain.…”

Role of the Cationic C-Terminal Segment of Melittin on Membrane Fragmentation

“…The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 specificity [10][11][12]63 . The stronger affinity of melittin for anionic than for neutral membranes had already been demonstrated [40][41]61 and is corroborated by the present results ( Figure 1).…”

“…Melittin-21Q exhibited a reduced or similar binding to DMPC and to DMPG bilayers compared to native melittin, suggesting a favorable or a limited contribution of the cationic C-terminal portion to membrane affinity. Another investigation, using tryptophan fluorescence, revealed that melittin and its Cterminal truncated versions , and [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], all showed an increased affinity for 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) 70/30 large unilamellar vesicles (LUVs) compared POPC LUVs 47 (See Supporting Information). These findings highlighted the role of attractive electrostatic interactions.…”

“…It is believed that the cationic charge of CAPs plays a fundamental role in the targeting of bacterial cells [10][11][12] as these typically possess negatively charged membranes 13 . For example, the increase of the net positive charge of synthetic CAPs was found to improve their antimicrobial activity while maintaining low toxicity towards mammalian cells 6,8 .…”