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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties

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Author(s):
Leite, Natalia Bueno [1] ; Aufderhorst-Roberts, Anders [2, 3] ; Palma, Mario Sergio [4, 5, 6] ; Connell, Simon D. [2, 3] ; Ruggiero Neto, Joao [1] ; Beales, Paul A. [7, 3]
Total Authors: 6
Affiliation:
[1] Univ Estadual Paulista, Sao Paulo State Univ, Dept Phys, Inst Biociencias Letras & Ciencias Exatas, Sao Paulo - Brazil
[2] Univ Leeds, Sch Phys & Astron, Leeds, W Yorkshire - England
[3] Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds, W Yorkshire - England
[4] Univ Estadual Paulista, Sao Paulo State Univ, Ctr Studies Social Insects, Sao Paulo - Brazil
[5] Univ Estadual Paulista, Sao Paulo State Univ, Dept Biol, Sao Paulo - Brazil
[6] Univ Estadual Paulista, Sao Paulo State Univ, Inst Biociencias, Sao Paulo - Brazil
[7] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire - England
Total Affiliations: 7
Document type: Journal article
Source: BIOPHYSICAL JOURNAL; v. 109, n. 5, p. 936-947, SEP 1 2015.
Web of Science Citations: 40
Abstract

Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is attributed to excess serine (phosphatidylserine (PS)) on the outer leaflet of cancer cells. Recently, higher quantities of phosphatidylethanolamine (PE) were also found at these cells' surface. We investigate the interaction of MP1 with model membranes in the presence and absence of POPS (PS) and DOPE (PE) to understand the role of lipid composition in MP1's anticancer characteristics. Indeed we find that PS lipids significantly enhance the bound concentration of peptide on the membrane by a factor of 7-8. However, through a combination of membrane permeability assays and imaging techniques we find that PE significantly increases the susceptibility of the membrane to disruption by these peptides and causes an order-of-magnitude increase in membrane permeability by facilitating the formation of larger transmembrane pores. Significantly, atomic-force microscopy imaging reveals differences in the pore formation mechanism with and without the presence of PE. Therefore, PS and PE lipids synergistically combine to enhance membrane poration by MP1, implying that the combined enrichment of both these lipids in the outer leaflet of cancer cells is highly significant for MP1's anticancer action. These mechanistic insights could aid development of novel chemotherapeutics that target pathological changes in the lipid composition of cancerous cells. (AU)

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