Selective assembly and insertion of ubiquicidin antimicrobial peptide in lipid monolayers

J Mater Chem B. 2024 Nov 20;12(45):11731-11745. doi: 10.1039/d4tb01487a.

Abstract

Antimicrobial-resistant bacteria pose a significant threat to humans, prompting extensive research into developing new antimicrobial peptides (AMPs). The biomembrane is the first barrier of a biological cell, hence, comprehending the interaction and self-assembly of AMPs in and around such membranes is of great importance. In the present study, several biophysical techniques have been applied to explore the self-assembly of ubiquicidin (29-41), an archetypical AMP, in and around the phospholipid monolayers formed at air-water interface. Such a monolayer mimics one of the leaflets of a lipid bilayer. The surface pressure-area isotherm exhibits the strongest interaction with a negatively charged lipid, 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG). The weakest affinity was towards the zwitterionic lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Another zwitterionic lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), shows an intermediate affinity. This affinity was quantified by analyzing alterations in the effective mean molecular area of the lipid, the in-plane compressional modulus of the assembly, and the electrostatic potential induced by the presence of peptides. The precise organization of the peptide around the lipid monolayer at a sub-nanometre length scale was revealed using synchrotron-based X-ray reflectivity measurements from the air-water interface. Information about the selective interaction of the peptide with lipids and their varied orientation at the lipid-water interface could be useful in understanding the selectivity of AMP in developing new antibiotics.

MeSH terms

  • Air
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Peptides* / chemistry
  • Antimicrobial Peptides* / pharmacology
  • Lipid Bilayers / chemistry
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylglycerols / chemistry
  • Surface Properties

Substances

  • Antimicrobial Peptides
  • Antimicrobial Cationic Peptides
  • Lipid Bilayers
  • Phosphatidylglycerols
  • Phosphatidylethanolamines