Lipid headgroup discrimination by antimicrobial peptide LL-37: insight into mechanism of action.
Interaction of the human antimicrobial peptide LL-37 with lipid monolayers has been investigated by a range of complementary techniques including pressure-area isotherms, insertion assay, epifluorescence microscopy, and synchrotron x-ray scattering, to analyze its mechanism of action. Lipid monolayers were formed at the air-liquid interface to mimic the surface of the bacterial cell wall and the outer leaflet of erythrocyte cell membrane by using phosphatidylglycerol (DPPG), phosphatidylcholine (DPPC), and phosphatidylethanolamine (DPPE) lipids. LL-37 is found to readily insert into DPPG monolayers, disrupting their structure and thus indicating bactericidal action. In contrast, DPPC and DPPE monolayers remained virtually unaffected by LL-37, demonstrating its nonhemolytic activity and lipid discrimination. Specular x-ray reflectivity data yielded considerable differences in layer thickness and electron-density profile after addition of the peptide to DPPG monolayers, but little change was seen after peptide injection when probing monolayers composed of DPPC and DPPE. Grazing incidence x-ray diffraction demonstrated significant peptide insertion and lateral packing order disruption of the DPPG monolayer by LL-37 insertion. Epifluorescence microscopy data support these findings.
Neville
Frances
F
Institute for Materials Research, University of Leeds, Leeds, United Kingdom.
Cahuzac
Marjolaine
M
Konovalov
Oleg
O
Ishitsuka
Yuji
Y
Lee
Ka Yee C
KY
Kuzmenko
Ivan
I
Kale
Girish M
GM
Gidalevitz
David
D
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D054804:Cathelicidins; D002473:Cell Wall / Q000378:metabolism; D046169:Dermoscopy; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D017356:Synchrotrons; D014961:X-Ray Diffraction
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; C030345:1,2-dipalmitoylphosphatidylglycerol