TY - JOUR

T1 - Self-assembly of spin-labeled antimicrobial peptides magainin 2 and PGLa in lipid bilayers

AU - Syryamina, Victoria N.

AU - Aisenbrey, Christopher

AU - Kardash, Maria

AU - Dzuba, Sergei A.

AU - Bechinger, Burkhard

N1 - We thank Elise Glattard for antimicrobial testing of the modified peptides. VNS and SAD are thankful to the Russian Science Foundation (project #21-13-00025) for the financial support. The financial contributions to the French laboratory of the Agence Nationale de la Recherche (projects Biosupramol 17-CE18-0033-3, Naturalarsenal 19-AMRB-0004-02, AmphiPep 20-CE18-0021 and the LabEx Chemistry of Complex Systems 10-LABX-0026_CSC), the University of Strasbourg, the CNRS, the R\u00E9gion Grand-Est and the Foundation Jean-Marie Lehn / Interdisciplinary Thematic Institute SysChem / IdEx Unistra (ANR-10-IDEX-0002) are gratefully acknowledged. We are grateful to the French Ambassy in the Russian Republic to have supported a co-tutorial PhD position.

PY - 2024/7

Y1 - 2024/7

N2 - he cationic antimicrobial peptides PGLa and magainin 2 (Mag2) are known for their antimicrobial activity and synergistic enhancement in antimicrobial and membrane leakage assays. Further use of peptides in combinatory therapy requires knowledge of the mechanisms of action of both individual peptides and their mixtures. Here, electron paramagnetic resonance (EPR), double electron-electron resonance (DEER, also known as PELDOR) and electron spin echo envelope modulation (ESEEM) spectroscopies were applied to study self-assembly and localization of spin-labeled PGLa and Mag2 in POPE/POPG membranes with a wide range of peptide/lipid ratios (P/L) from ∼1/1500 to 1/50. EPR and DEER data showed that both peptides tend to organize in clusters, which occurs already at the lowest peptide/lipid molar ratio of 1/1500 (0.067 mol%). For individual peptides, these clusters are quite dense with intermolecular distances of the order of ∼2 nm. In the presence of a synergistic peptide partner, these homo-clusters are transformed into lipid-diluted hetero-clusters. These clusters are characterized by a local surface density that is several times higher than expected from a random distribution. ESEEM data indicate a slightly different insertion depth of peptides in hetero-clusters when compared to homo-clusters.

AB - he cationic antimicrobial peptides PGLa and magainin 2 (Mag2) are known for their antimicrobial activity and synergistic enhancement in antimicrobial and membrane leakage assays. Further use of peptides in combinatory therapy requires knowledge of the mechanisms of action of both individual peptides and their mixtures. Here, electron paramagnetic resonance (EPR), double electron-electron resonance (DEER, also known as PELDOR) and electron spin echo envelope modulation (ESEEM) spectroscopies were applied to study self-assembly and localization of spin-labeled PGLa and Mag2 in POPE/POPG membranes with a wide range of peptide/lipid ratios (P/L) from ∼1/1500 to 1/50. EPR and DEER data showed that both peptides tend to organize in clusters, which occurs already at the lowest peptide/lipid molar ratio of 1/1500 (0.067 mol%). For individual peptides, these clusters are quite dense with intermolecular distances of the order of ∼2 nm. In the presence of a synergistic peptide partner, these homo-clusters are transformed into lipid-diluted hetero-clusters. These clusters are characterized by a local surface density that is several times higher than expected from a random distribution. ESEEM data indicate a slightly different insertion depth of peptides in hetero-clusters when compared to homo-clusters.

KW - EPR

KW - Lipid-mediated peptide clusters

KW - Peptides

KW - Synergy

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85191333616&origin=inward&txGid=24e2648e8d248aec92ccf63f02d7a141

UR - https://www.mendeley.com/catalogue/597a308a-3c52-39d1-8de1-905bebfc66fd/

U2 - 10.1016/j.bpc.2024.107251

DO - 10.1016/j.bpc.2024.107251

M3 - Article

C2 - 38678820

VL - 310

JO - Biophysical Chemistry

JF - Biophysical Chemistry

SN - 0301-4622

M1 - 107251

ER -