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Bicontinuous inverted cubic phase formation as a predictor of antimicrobial and fusion peptide activity

2022; Elsevier BV; Volume: 121; Issue: 3 Linguagem: Inglês

10.1016/j.bpj.2021.11.1622

1542-0086

David P. Siegel,

Biochemical and Structural Characterization

Some antimicrobial peptides (AMPs) and membrane fusion-catalyzing peptides (FPs) stabilize bicontinuous inverted cubic (QII) phases. Previous authors proposed a topological rationale for this correlation: AMP-induced pores, fusion intermediates, and QII phases all have negative Gaussian curvature (NGC). This rationale implicitly assumes that peptides change the curvature energy of lipid membranes. Here I test the proposed rationale, using simple models of the curvature energy of the QII phase and of the relevant intermediate structures. First, it is shown experimentally that model lipid systems which were often used in experiments on NGC induction form sponge or QII phases with NGC in the absence of peptides, at slightly higher temperatures. It is important to establish the equilibrium phase behavior in the presence and absence of peptide, to determine the net effect of a peptide. Second, the curvature energy models show that AMP-induced changes in given elastic constants would affect the stability of AMP-induced pores and QII phases in different ways. In particular, changes in spontaneous curvature affect the stability of AMP-induced pores and QII phase in opposite ways. The correlation between QII phase stabilization and AMP activity, by itself, does not establish a curvature energy reduction mechanism for AMP action. A different rationale for the observed correlation is proposed. In theory AMPs could simultaneously stabilize QII phase and AMP-induced pores by making drastic changes in two particular curvature elastic constants (changing their signs). A test of this hypothesis would be to measure AMP effects on the individual curvature elastic constants. I propose experiments to do that. In contrast to the case with AMPs, the curvature energy model suggests that FP activity should correlate with QII phase stabilization.