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

Author(s)

Alvares, Dayane S. ; Wilke, Natalia ; Ruggiero Neto, Joao ; Fanani, Maria Laura

• Document type: Journal article
• Source: Chemistry and Physics of Lipids; v. 207, p. 11-pg., 2017-10-01.

Abstract

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)

• FAPESP's process: 15/25620-7 - Interaction membrane/peptide: mechanical and electrostatic properties in system with lipid domains
• Grantee: Dayane dos Santos Alvares
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/08147-8 - Study of domains formation in model membranes induced by antimicrobial peptides and their action interfacial
• Grantee: Dayane dos Santos Alvares
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/11640-5 - Interaction of lytic peptides and model membranes: intefacial action and induction of lipid domains
• Grantee: João Ruggiero Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/51684-1 - System biology as experimental strategy for discovery of novel natural products in the fauna of venomous arthropods from São Paulo State
• Grantee: Mario Sergio Palma
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 15/01508-3 - Interaction of the antimicrobial and antitumor peptide, Polybia-MP1, with lipid-domains
• Grantee: Dayane dos Santos Alvares
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 15/25619-9 - Effect of aminophospholipids and of the pH on the interfacial activity of the anticancer peptide Polybia-MP1 and analogs in model membranes
• Grantee: João Ruggiero Neto
• Support Opportunities: Regular Research Grants