Work

Leaflet-Dependent Effect of Anionic Lipids on Membrane Insertion by Cationic Cell-Penetrating Peptides

Year: 2023

Type: article

Abstract: Cationic membrane-permeating peptides can cross membranes unassisted by transmembrane protein machinery, and there is consensus that anionic lipids facilitate this process. Although membranes are asymmetric in lipid composition, investigations of the impact of anionic lipids on peptide–membrane insertion in model vesicles primarily use symmetric anionic lipid distributions between bilayer leaflets. Here, we investigate the leaflet-specific influence of three anionic lipid headgroups [phosphatidic acid (PA), phosphatidylserine (PS), and phosphatidylglycerol (PG)] on insertion into model membranes by three cationic membrane-permeating peptides (NAF-1 44–67, R 6 W 3, and WWWK). We report that outer leaflet anionic lipids enhanced peptide–membrane insertion for all peptides while inner leaflet anionic lipids did not have a significant effect except in the case of NAF-1 44–67 incubated with PA-containing vesicles. The insertion enhancement was headgroup-dependent for arginine-containing peptides but not WWWK. These results provide significant new insight into the potential role of membrane asymmetry in insertion of peptides into model membranes.

Source: The Journal of Physical Chemistry Letters

DOI: 10.1021/acs.jpclett.3c00725

Authors: Sydney C. Povilaitis, Lauren J. Webb

Institution: The University of Texas at Austin

Language: English

Topic: Lipid Membrane Structure and Behavior

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Welch Foundation, University of Texas at Austin, National Institutes of Health, National Institute of General Medical Sciences

Awards: Modeling Membrane Dynamics and Permeation, G2068707083, G3642223645, G7278145822