Concentration-Dependent Modes of Melittin-Induced Membrane Destabilization: An Integration of Experimental and Computational Tools.
- 1Department of Chemistry & CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro3810-193, Portugal.
- 2Department of Physics & CICECO-Aveiro Institute of Materials, University of Aveiro, Aveiro3810-193, Portugal.
- 3São Carlos Institute of Physics, University of São Paulo, CP 369, São Carlos, São Paulo13560-970, Brazil.
Abstract
Melittin is a well-known antimicrobial peptide whose mechanism of action is still not entirely understood. In this study, we combine complementary experimental techniques with molecular dynamics simulations to determine melittin-membrane interactions at different scales. Using 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE): 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) membranes that mimic the Escherichia coli inner membrane, this integrative approach reveals a clear transition in melittin's mode of action with increasing peptide loading. At low concentrations, melittin primarily perturbs the membrane interface, inducing modest surface expansion and subtle lipid reorganization. At higher concentrations, the membrane response shifts toward increased hydration, lipid disorder, membrane thinning, and morphological remodeling. Simulations support these observations, linking concentration-dependent membrane responses to enhanced lipid mobility and stronger effects on anionic DPPG. Melittin, therefore, affects the membrane in a concentration-dependent manner, transitioning from surface-bound carpet-like permeabilization at low loading to transient pore formation and membrane reorganization at higher concentrations.
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BibTeX
@article{calderon2026concentrationdependent,
title = {{Concentration-Dependent Modes of Melittin-Induced Membrane Destabilization: An Integration of Experimental and Computational Tools.}},
author = {Andrea Chacón Calderón and Pavel Zelenovskii and Márcio Soares and Ellen C Wrobel and Osvaldo N Oliveira and Daniel Pereira and Mariana Sardo and Luís Mafra and Ana Barros-Timmons and Ildefonso Marín-Montesinos},
journal = {Langmuir : the ACS journal of surfaces and colloids},
year = {2026},
month = sep,
doi = {10.1021/acs.langmuir.6c02887},
url = {https://europepmc.org/article/MED/42918005},
note = {CC BY},
}
RIS
TY - JOUR
TI - Concentration-Dependent Modes of Melittin-Induced Membrane Destabilization: An Integration of Experimental and Computational Tools.
AU - Andrea Chacón Calderón
AU - Pavel Zelenovskii
AU - Márcio Soares
AU - Ellen C Wrobel
AU - Osvaldo N Oliveira
AU - Daniel Pereira
AU - Mariana Sardo
AU - Luís Mafra
AU - Ana Barros-Timmons
AU - Ildefonso Marín-Montesinos
PY - 2026
DA - 2026/09/01
JO - Langmuir : the ACS journal of surfaces and colloids
DO - 10.1021/acs.langmuir.6c02887
UR - https://europepmc.org/article/MED/42918005
AB - Melittin is a well-known antimicrobial peptide whose mechanism of action is still not entirely understood. In this study, we combine complementary experimental techniques with molecular dynamics simulations to determine melittin-membrane interactions at different scales. Using 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE): 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) membranes that mimic the Escherichia coli inner membrane, this integrative approach reveals a clear transition in melittin's mode of action with increasing peptide loading. At low concentrations, melittin primarily perturbs the membrane interface, inducing modest surface expansion and subtle lipid reorganization. At higher concentrations, the membrane response shifts toward increased hydration, lipid disorder, membrane thinning, and morphological remodeling. Simulations support these observations, linking concentration-dependent membrane responses to enhanced lipid mobility and stronger effects on anionic DPPG. Melittin, therefore, affects the membrane in a concentration-dependent manner, transitioning from surface-bound carpet-like permeabilization at low loading to transient pore formation and membrane reorganization at higher concentrations.
SN - 0743-7463
SN - 1520-5827
ER -