Lactoferrin-derived antimicrobial peptide induces a micellar cubic phase in a model membrane system

Abstract

The observation of a micellar cubic phase is reported for a mixture of an antimicrobial peptide from the Lactoferrin family, LFampin 265-284, and a model membrane system of dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (3:1), as derived from small-angle x-ray diffraction (SAXD) measurements. The system shows remarkable thermotropic polymorphism: the peptide disrupts the lipid bilayer, forming a cubic phase of the space group Pm3n (t < 28°C), and as the temperature increases it shows a complex phase behavior (not fully clarified by SAXD). The onset, volume fraction of each phase, and phase parameters are seen to vary with peptide/lipid ratio and temperature. The obtained SAXD data represent the first experimental evidence, to our knowledge, of a micellar cubic phase in the context of antimicrobial peptide/membrane interaction. We propose that the micellization of the membrane according to the carpet model, for long proposed as a possible mechanism of action, can go through the formation of a cubic micellar phase.

Figure 1

SAXD patterns for P/L mixture 1:5 (mol/mol) at selected temperatures. (Inset) Pm3n unit cell.

Figure 2

SAXD patterns for P/L mixture 1:8 at selected temperatures. The peak at position √6 is systematically absent. (Inset) A plot of s = f(sqrt(h² + k² + l²)) for all observed reflections at 24°C.