Leaflet by Leaflet Synergistic Effects of Antimicrobial Peptides on Bacterial and Mammalian Membrane Models

Abstract

Antimicrobial peptides (AMPs) offer significant hope in the fight against antibiotic resistance. Operating via a mechanism different from that of antibiotics, they target the microbial membrane and ideally should damage it without impacting mammalian cells. Here, the interactions of two AMPs, magainin 2 and PGLa, and their synergistic effects on bacterial and mammalian membrane models were studied using electrochemical impedance spectroscopy, atomic force microscopy (AFM), and fluorescence correlation spectroscopy. Toroidal pore formation was observed by AFM when the two AMPs were combined, while individually AMP effects were confined to the exterior leaflet of the bacterial membrane analogue. Using microcavity-supported lipid bilayers, the diffusivity of each bilayer leaflet could be studied independently, and we observed that combined, the AMPs penetrate both leaflets of the bacterial model but individually each peptide had a limited impact on the proximal leaflet of the bacterial model. The impact of AMPs on a ternary, mammalian mimetic membrane was much weaker.

Hybrid bio-nanoporous peptide loaded-polymer platforms with anticancer and antibacterial activities

“…The affinity of AMPs for cancer cells is weaker compared to that of the bacteria due to a low density of negative charges present on mammalian cell surface and the rigidifying effect induced by cholesterol on the membrane. 74,75 The multifunctional capacity of AMPs raised the interest for their applications as antimicrobial and antitumor drugs. In this respect, several studies focused on the evaluation of combinatory treatment potential on a stronger effect than that of individual cationic peptide, most of the investigations being performed from a microbiological point of view and less on the antitumor activity.…”

Triplet–Triplet Annihilation Upconverting Liposomes: Mechanistic Insights into the Role of Membranes in Two-Dimensional TTA-UC

“…The lipid membrane is a suitable platform to confine the photosensitizer and annihilator to the same plane assuming both species localize to the same region of the membrane, and that their orientation is conducive to energy transfer. To that end, we first prepared large unilamellar vesicles (LUVs) − (hydrodynamic diameter ∼140 ± 5 nm from DLS) of DOPC and two different giant unilamellar vesicles (GUVs), comprising DOPC only and a ternary phase-separated DOPC:SM (sphingomyelin):Chol (2:2:1). From imaging, GUVs were ∼10–30 μm doped with B2P- and B2PI–perylene pairs.…”

“…The DOPC lipid bilayer was spanned across aqueous-filled PDMS microcavities to form the microcavity-supported lipid bilayer. Initially, the lipid monolayer was transferred using the Langmuir–Blodgett (LB) technique at the air–water interface as reported previously, − whereby a 1 mg/mL lipid solution in cholesterol was added to the water subphase of an LB trough (NIMA 102D) and the solvent was allowed to evaporate for about 10 min. The lipid monolayer was transferred to the microcavities at a 33 mN/m surface pressure.…”

N-formylation modifies membrane damage associated to PSMα3 interfacial fibrillation

“…As our ATR-FTIR data do not support a change in membrane fluidity and organization, such pores would result from a barrelstave pore model, where the amphipathic structure of PSMα3 favours interactions between its hydrophobic residues and the lipid acyl chains and preserve the hydrophilic lipid head group arrangement 58 . Such a mix between a carpet-like and a pore formation models has been described for some AMP that, after accumulating at a critical concentration on bacterial membranes, disrupt their integrity by two-dimensional lateral diffusion within the membrane, illustrated via AFM imaging by holes spanning the full or partial (the outer leaflet) bilayer or only a thinning effect [59][60][61] .…”