Deciphering Solution and Gas-Phase Interactions between Peptides and Lipids by Native Mass Spectrometry

Area of Science:

• Biochemistry
• Biophysics
• Analytical Chemistry

Background:

• Protein-lipid interactions are crucial for many biological processes.
• Native mass spectrometry is a key technique for studying these interactions.
• The transfer of analytes to the gas phase raises questions about the accuracy of observed interactions.

Purpose of the Study:

• To systematically explore noncovalent interactions between the antimicrobial peptide LL-37 and glycerophospholipids.
• To determine whether gas-phase observations accurately reflect solution-phase interactions.
• To differentiate the influence of electrostatic and hydrophobic interactions on observed complexes.

Main Methods:

• Systematic exploration of noncovalent interactions between LL-37 and various glycerophospholipids.
• Analysis of peptide-lipid complexes using native mass spectrometry.
• Varying lipid headgroups and fatty acyl chain lengths to probe different interaction types.

Main Results:

• Observed differences in peak intensities and relative binding strength for various peptide-lipid complexes in the gas phase.
• Ion intensities correlated well with electrostatic interactions, while hydrophobic interactions were reflected by ion intensities.
• Gas-phase stability was primarily determined by electrostatic and van der Waals interactions.

Conclusions:

• Hydrophobic interactions are reflected by ion intensities in native mass spectrometry.
• Electrostatic interactions, including van der Waals forces, dictate gas-phase stability.
• Native mass spectrometry can provide insights into both hydrophobic and electrostatic aspects of protein-lipid interactions.