PE and PS lipids synergistically enhance membrane poration by a peptide with anticancer properties

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorLeite, Natália Bueno
dc.creatorAufderhorst-Roberts, Anders
dc.creatorPalma, Mário Sérgio
dc.creatorConnell, Simon D.
dc.creatorNeto, João Ruggiero
dc.creatorBeales, Paul A.
dc.date2015-12-07T15:37:23Z
dc.date2016-10-25T21:23:48Z
dc.date2015-12-07T15:37:23Z
dc.date2016-10-25T21:23:48Z
dc.date2015-09-01
dc.date.accessioned2017-04-06T09:31:28Z
dc.date.available2017-04-06T09:31:28Z
dc.identifierBiophysical Journal, v. 109, n. 5, p. 936-947, 2015.
dc.identifier1542-0086
dc.identifierhttp://hdl.handle.net/11449/131549
dc.identifierhttp://acervodigital.unesp.br/handle/11449/131549
dc.identifier10.1016/j.bpj.2015.07.033
dc.identifierPMC4564682.pdf
dc.identifier26331251
dc.identifierPMC4564682
dc.identifierhttp://dx.doi.org/10.1016/j.bpj.2015.07.033
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/942089
dc.descriptionPolybia-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.
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageeng
dc.publisherElsevier B. V.
dc.relationBiophysical Journal
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlePE and PS lipids synergistically enhance membrane poration by a peptide with anticancer properties
dc.typeOtro


Este ítem pertenece a la siguiente institución