resumo
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.
autores
Andrea Chacón Calderón; Pavel Zelenovskii; Márcio Soares; Ellen C. Wrobel; Osvaldo N. Oliveira Jr; Daniel Pereira; Mariana Sardo; Luís Mafra; Ana Barros-Timmons ; Ildefonso Marín-Montesinos
nossos autores
Ana Margarida Madeira Viegas de Barros Timmons
Professor associado
Andrea Chacón Calderón
Estudante de doutoramento
Ildefonso Marin Montesinos
Investigador Auxiliar
Luís Mafra
Investigador Principal
Márcio Miguel da Silva Soares
Estudante de doutoramento
Mariana Coutinho Sardo
Investigador Auxiliar
Pavel Zelenovskii
InvestigadorGrupos
G1 - Materiais Porosos e Nanossistemas
G3 - Materiais Eletroquímicos, Interfaces e Revestimentos
G4 - Materiais Renováveis e Economia Circular
Projectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020), and LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) financed by national funds through the FCT/MEC (PIDDAC). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by the Infrastructure Project 022161 (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 865974) and from CNPq and FAPESP (2025/27044-5 and 2020/15571-7) (Brazil).