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

Biophysical Journal
Natália Bueno LeitePaul A Beales

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 ca...Continue Reading

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Citations

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Sep 12, 2019·Biochemistry·Marcos Arribas PerezPaul A Beales

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Methods Mentioned

BETA
confocal microscopy
circular
atomic-force microscopy
gel filtration
AFM
fluorescence microscopy
Fluorescence

Software Mentioned

MASSLYNX
IMAGEJ
TRANSFORM

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