Mechanism of membrane disruption by antimicrobial peptides (AMPs)

Current: ______ (Open project!)
Alumni: Michael Henderson, Nishanth Iyengar

Antimicrobial peptides (AMPs) are a class of small host defense peptides that induce selective membrane lytic activity against microbial pathogens through the formation of pores.

Using lipid bilayer patches supported on a mica substrate, AMP interactions with membranes can be probed using AFM.

Protegrin-1 (PG-1) is a cationic β-sheet 18-amino acid peptide isolated from porcine leukocytes that exhibits potency against several gram-negative and gram-positive bacteria, fungi and viruses.

In the absence of peptide (A) the bilayer patches are compact in shape and display smooth boundaries maintained by a high interfacial line tension. As the bulk peptide concentration is increased, the smooth contours of the patches are rendered rough as peptide adsorption at the membrane edge reduces the interfacial tension (B). Eventually the lamellar interior of the patch is compromised as pores (C) and worm-like micelles (D) span the entire depth of the bilayer.

Other AMPs with different molecular characteristics display the same type of structural transformations as seen for PG-1.

Cholesterol is a major component in mammalian cell membranes but nonexistent in bacterial cell membranes. AMPs may be able to sense specific membrane compositional differences allowing them to target pathogens while leaving host cells intact.

Selected bibliography

Gidalevitz, D. et al. PNAS 100, 6302–6307 (2003). https://doi.org/10.1073/pnas.0934731100
Lam, K. L. H. et al. BBA – Biomembranes 1818, 194–204 (2012). https://doi.org/10.1016/j.bbamem.2011.11.002
Henderson, J. M. & Lee, K. Y. C. Curr. Opin. Solid State and Mater. Sci. 17, 175–192 (2013). http://dx.doi.org/10.1016/j.cossms.2013.08.003