PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties
| Autor: | Anders Aufderhorst-Roberts, Natália Bueno Leite, João Ruggiero Neto, Simon D. Connell, Mario Sergio Palma, Paul A. Beales |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), University of Leeds |
| Rok vydání: | 2015 |
| Předmět: |
Cell Membrane Permeability
Membrane permeability Biophysics Peptide Antineoplastic Agents Wasp Venoms Phosphatidylserines Serine Cell membrane chemistry.chemical_compound medicine Unilamellar Liposomes chemistry.chemical_classification Membranes Dose-Response Relationship Drug Phosphatidylethanolamines Cell Membrane Phosphatidylserine Transmembrane protein Kinetics Membrane medicine.anatomical_structure chemistry Biochemistry Cancer cell Porosity Antimicrobial Cationic Peptides |
| Zdroj: | PubMed Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1542-0086 0006-3495 |
| Popis: | Made available in DSpace on 2015-12-07T15:37:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-01. Added 1 bitstream(s) on 2015-12-07T15:53:13Z : No. of bitstreams: 1 PMC4564682.pdf: 1657566 bytes, checksum: ff0dc42896c4b04166a3d70e68a4f8e9 (MD5) Biomedical and Health Research Centre at the University of Leeds European Union Marie Curie Career Integration Grant BioNanoMuTT Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Engineering and Physical Sciences Research Council 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. Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brasil School of Physics and Astronomy and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK Centro de Estudos de Insetos Sociais (CEIS), Departamento de Biologia, Instituto de Biociências de Rio Claro (IBRC), Universidade Estadual Paulista (UNESP), Rio Claro, SP, Brasil Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brasil School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK Universidade Estadual Paulista, Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas de São José do Rio Preto Universidade Estadual Paulista, Centro de Estudos de Insetos Sociais de Rio Claro Universidade Estadual Paulista, Departamento de Biologia, Instituto de Biociências de Rio Claro European Union Marie Curie Career Integration Grant BioNanoMuTT: PCIG09-GA-2011-293643 FAPESP: 2011/11640-5 FAPESP: 2011/51684-1 Engineering and Physical Sciences Research Council: EP/J017566/1 |
| Databáze: | OpenAIRE |
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