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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The insertion of Polybia-MP1 peptide into phospholipid monolayers is regulated by its anionic nature and phase state

Texto completo
Autor(es):
Alvares, Dayane S. ; Wilke, Natalia ; Ruggiero Neto, Joao ; Fanani, Maria Laura
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: Chemistry and Physics of Lipids; v. 207, n. A, p. 38-48, OCT 2017.
Citações Web of Science: 8
Resumo

Polybia-MP1 or simply MP1 (IDWKKLLDAAKQIL-NH2) is a peptide with broad-spectrum bactericidal activity and a strong inhibitory effect against cancer cells. The aim of this work was to evaluate the effect of biophysical properties such as membrane texture and film thickness on MP1 interaction with neutral and anionic lipid membranes. For this purpose, we first explored the peptide's surface behavior. MP1 showed high surface activity, adsorbing onto bare air/aqueous interfaces up to higher surface pressures than the collapse pressure of MP1 Langmuir films. The MPl-lipid membrane interaction was studied using Langmuir phosphatidylcholine and phosphatidylseririe (PS) monolayers as model membrane systems. PS was chosen since this negatively charged lipid was found predominantly on the outer leaflet of tumor cells, and it enhances MP1 activity for PS-containing membranes to a greater extent than for other negatively charged lipids. MP1 incorporated into anionic PS monolayers, which show a liquid-expanded (LE) phase or LE-liquid -condensed (LC) phase coexistence, up to lipid-packing densities higher than those of cell membranes. The mixed lipid/MP1 films were explored by Brewster angle microscopy and atomic force microscopy. MP1 partitioned preferentially into the LE phase state of PS films, and were thus excluded from the coexisting LC phase. This interaction had strong electrostatic bases: in pure water, the lipid-peptide interaction was strong enough to induce formation of reversible lipid-peptide 3D structures associated with the interface. MP1 incorporation into the LE phase was accompanied by a shift of the phase transition pressure to higher values and a thinning of the lipid film. These results showed a clear correlation between peptide penetration capacity and the presence or induction of the thin LE phase. This capacity to regulate membrane physical properties may be of relevance in the binding, incorporation and membrane selectivity of this promising antitumor peptide. (AU)

Processo FAPESP: 11/51684-1 - Biologia de sistemas como estratégia experimental para a descoberta de novos produtos naturais na fauna de artrópodes peçonhentos do Estado de São Paulo
Beneficiário:Mario Sergio Palma
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
Processo FAPESP: 12/08147-8 - Estudo da formação de domínios em membranas modelo induzidos por peptídeos antimicrobianos e sua ação interfacial
Beneficiário:Dayane dos Santos Alvares
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 11/11640-5 - Interação de peptídeos líticos e membranas modelo: ação interfacial e indução de domínios lipídicos
Beneficiário:João Ruggiero Neto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/25619-9 - Efeito de aminofosfolípides e do pH na atividade interfacial do peptídeo anticâncer Polybia-MP1 e análogos em membranas modelo
Beneficiário:João Ruggiero Neto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/01508-3 - Interação do peptídeo antimicrobiano e antitumoral, Polybia-MP1, com domínios lipídicos
Beneficiário:Dayane dos Santos Alvares
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 15/25620-7 - Interação membrana/peptídeo: propriedades mecânica e eletrostática em sistemas com domínios lipídicos
Beneficiário:Dayane dos Santos Alvares
Linha de fomento: Bolsas no Brasil - Pós-Doutorado