Mechanism of supported membrane disruption by antimicrobial peptide protegrin-1

Kin Lok H Lam1, Yuji Ishitsuka, Yishan Cheng

  • 1Department of Physics, The Institute for Biophysical Dynamics, and The James Franck Institute, The University of Chicago, Illinois 60637, USA.

Insights

Antimicrobial peptide protegrin-1 (PG-1) directly visualizes membrane disruption. PG-1 concentration dictates membrane changes, forming fingerlike, nanoporous, or stripelike structures, revealing its disruption mechanism.

Area of Science:

  • Biophysics
  • Membrane Biology
  • Antimicrobial Peptides

Background:

  • Antimicrobial peptides (AMPs) are crucial for innate immunity.
  • Membrane disruption is a proposed mechanism for AMP action.
  • Direct visualization of AMP-induced membrane pore formation has been lacking.

Purpose of the Study:

  • To directly visualize the membrane disruption dynamics induced by the antimicrobial peptide protegrin-1 (PG-1).
  • To elucidate the concentration-dependent mechanism of PG-1-induced membrane alteration.

Main Methods:

  • Atomic force microscopy (AFM) was used to observe supported lipid bilayer patches.
  • Dimyristoyl-sn-glycero-phosphocholine (DMPC) lipid bilayers were employed.
  • Real-time imaging captured the structural transformations upon PG-1 addition.

Main Results:

  • PG-1 induced concentration-dependent membrane structural changes.
  • Low PG-1 concentrations (<4 microg/mL) led to edge destabilization and fingerlike structures.
  • Higher PG-1 concentrations induced nanoporous or stripelike membrane structures, with complete disruption at >=20 microg/mL.

Conclusions:

  • This study provides the first direct visualization of antimicrobial peptide-induced membrane disruption.
  • The findings reveal a concentration-dependent mechanism for PG-1 action on lipid bilayers.
  • Understanding these dynamics is key to developing new antimicrobial peptide-based therapies.

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