Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly

Lawrence R. Walker, Elaine M. Marzluff, Julia A. Townsend, William C. Resager, Michael T. Marty

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Antimicrobial peptides (AMPs) are generally cationic and amphipathic peptides that show potential applications to combat the growing threat of antibiotic resistant infections. AMPs are known to interact with bacterial membranes, but their mechanisms of toxicity and selectivity are poorly understood, in part because it is challenging to characterize AMP oligomeric complexes within lipid bilayers. Here, we used native mass spectrometry to measure the stoichiometry of AMPs inserted into lipoprotein nanodiscs with different lipid components. Titrations of increasing peptide concentration and collisional activation experiments reveal that AMPs can exhibit a range of behaviors from nonspecific incorporation into the nanodisc to formation of specific complexes. This new approach to characterizing formation of AMP complexes within lipid membranes will provide unique insights into AMP mechanisms.

Original languageEnglish (US)
Pages (from-to)9284-9291
Number of pages8
JournalAnalytical Chemistry
Volume91
Issue number14
DOIs
StatePublished - Jun 18 2019

ASJC Scopus subject areas

  • Analytical Chemistry

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