Membrane orientation of MSI-78 measured by sum frequency generation vibrational spectroscopy

Pei Yang1, Ayyalusamy Ramamoorthy, Zhan Chen

  • 1Biophysics and Department of Chemistry, 930 North University Avenue, University of Michigan, Ann Arbor, Michigan 48109, USA.

Insights

Antimicrobial peptides (AMPs) like pexiganan selectively target bacterial membranes. Sum frequency generation spectroscopy revealed pexiganan

Area of Science:

  • Biophysics
  • Membrane Biophysics
  • Spectroscopy

Background:

  • Antimicrobial peptides (AMPs) exhibit selective disruption of bacterial cell membranes over mammalian cells.
  • Understanding AMP-lipid interactions is crucial for elucidating their antimicrobial activity and selectivity.

Purpose of the Study:

  • To determine the membrane orientation of the antimicrobial peptide MSI-78 (pexiganan) in various model membranes.
  • To investigate the role of AMP-lipid interactions in the functional properties and selectivity of MSI-78.

Main Methods:

  • Utilized sum frequency generation (SFG) vibrational spectroscopy to analyze peptide-lipid interactions.
  • Employed solid-supported lipid bilayers mimicking bacterial (DPPG, POPG) and mammalian (DPPC, POPC) cell membranes.
  • Varied peptide concentration to observe concentration-dependent effects on membrane orientation.

Main Results:

  • MSI-78 associated with negatively charged bacterial membranes (DPPG) with a surface orientation (∼70° tilt).
  • Increased MSI-78 concentration on DPPG led to a more perpendicular orientation (∼25° tilt) and pore formation.
  • No significant interaction was observed between MSI-78 and zwitterionic mammalian membranes (DPPC) even at high concentrations.
  • Concentration-dependent membrane orientation and toroidal-type pore formation were observed in POPG bilayers.

Conclusions:

  • SFG spectroscopy provides valuable insights into the antibacterial activity and selectivity of MSI-78.
  • MSI-78's membrane orientation and interaction are concentration-dependent and specific to membrane charge.
  • The findings support the mechanism of toroidal-type pore formation induced by MSI-78 in bacterial membranes.

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