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Inverted Cubic (QII) Phase Stabilizing Effects of Membrane Active Peptides as an Index of Antimicrobial Peptide (AMP) and Fusion Peptide Activity

2020; Elsevier BV; Volume: 118; Issue: 3 Linguagem: Inglês

10.1016/j.bpj.2019.11.3020

1542-0086

David P. Siegel,

Bacteriophages and microbial interactions

The ability of viral fusion peptides to stabilize QII phases correlates with peptide fusion activity [1]. AMP stabilization of QII phases has also been invoked as a measure of AMP activity [e.g., 2] in stabilizing bilayer membrane-spanning pores (MSPs). The AMPs were said to “induce NGC” (negative Gaussian curvature) of the composition. Here, I use a curvature elastic energy model of lipid-peptide monolayers to show that peptides which stabilize QII phases should also stabilize membrane fusion intermediates: the curvature energy expressions all have the same form. However, there is a poorer correlation for AMPs: e.g., peptides inducing more positive monolayer spontaneous curvature stabilize MSPs but de-stabilize QII. Moreover, previously the magnitude of the effect of AMPs on NGC was quantified only by the lattice constant, c, of the mixed QII phase [e.g., 2]. The propensity of the host lipid itself to form QII must be accounted for. One lipid system used to measure AMP effects on NGC [2] forms QII phases in the absence of peptide [5,6]; as do bacterial lipid extracts [7]. Details of the incubation conditions can substantially change c [3,4], but these are not always reported. I propose a more quantitative protocol for quantitatively comparing the effects of peptides on the energy of all these structures. One must measure peptide effects on HII & QII phases lattice constants over a temperature interval; the monolayer bending modulus; and the bilayer thickness. [1] Tenchov & Lentz, Biophys. J. 104:1029 (2013); [2] Lee et al., PNAS 113;13588 (2016); [3] Langmuir 26:8673 (2010); Biophys. J. 95:5200 (2008); [4] Eur. Biophys. J. 41:841 (2012); [5] Biophys. J. 78:2475 [2000]; [6] J. Phys. Chem. 115:8474 (2011); [7] BBA 1468:213 (2000).