Simultaneous modeling of phase and calorimetric behavior in an amphiphilic peptide phospholipid model membrane

Abstract

Differential scanning calorimetry (DSC) experiments have been performed on the amphiphilic peptide/1,2-bis(perdeuteriopalmitoyl)-sn-glycero-3-phosphocholine system for which partial phase diagrams have been measured by deuterium nuclear magnetic resonance. The solute concentration dependence of the transition enthalpy in such systems is often interpreted in terms of an annulus of lipid withdrawn, by the solvent, from participation in the transition while the bulk lipid melts with its fully enthalpy. This idea is equivalent to postulating ideal mixing between the lipid and the peptide/lipid complex, and there is little justification for such an assumption. Adaptation of regular solution theory to this system demonstrates that the peptide concentration dependence of the transition enthalpies can be incorporated into a thermodynamic model which reproduces the observed phase behavior fairly well without postulating that a complexing annulus of lipid around the peptide be withdrawn from participating in the chain-melting transition. The model parameters determined by simultaneous fitting of the phase behavior and transition enthalpies are used to simulate the DSC scan shapes. The asymmetry of the calorimetric scans for chi 2 less than or equal to 0.02 is reproduced by the model, but a broad component observed for higher concentration is not. In light of the results presented here, previous analyses of the calorimetric behavior of two-component systems in terms of symmetric transitions which do not account for the possible extent of a region of two-phase equilibrium must be questioned.

FTIR spectroscopic studies of the conformation and amide hydrogen exchange of a peptide model of the hydrophobic transmembrane .alpha.-helixes of membrane proteins

“…Our approach involves monitoring changes in the conformation of the peptide by an examination of the conformationally sensitive amide I band near 1650 cm-l and a study of the exchangeability of the amide protons of P24 by an examination of changes in both the amide I and amide I1 bands when samples of proteated P24 are dissolved in deuterated methanol. The data obtained should assist the interpretation of previous studies of the interaction of P24 with DPPC bilayers Morrow et al, 1985;Pauls et al, 1985;Roux et al, 1989) and the accompanying DSC and FT-IR spectroscopic study (Zhang et al, 1992).…”

Mechanical Properties of Bilayer Lipid Membranes and Protein–Lipid Interactions

“…[54,55]). In fact, circular dichroism (CD) [58] and FTIR [59] spectroscopic studies of P 24 have shown that it adopts a very stable a-helical conformation both in solution and in lipid bilayers, and X-ray diffraction [60], fluorescence quenching [61], FTIR [59], and deuterium nuclear magnetic resonance ( 2 H-NMR) [62] spectroscopic studies have confirmed that P 24 and its analogs assume a transbilayer orientation with the N-and C-termini exposed to the aqueous environment and the hydrophobic polyleucine core embedded in hydrocarbon core of the BLM when reconstituted with various PCs [63]. The synthetic peptide acetyl-K 2 -G-L 24 -K 2 -A-amide (P 24 ) and its structural analogs, for example, acetyl-K 2 -L 24 -K 2 -amide (L 24 ), have been successfully utilized as a model of the hydrophobic transmembrane a-helical segments of integral proteins [55,58].…”

Transmembrane α helices

“…A number of studies have been published on the effects of these peptides on the phase transition properties of lipid bilayers. Addition of the peptide PI6 to bilayers of di(CI6:0)PC both broadens the main gel-to-liquid crystalline phase transition and decreases the enthalpy of the transition (Morrow et al, 1985). Similar effects have been seen on incorporation of membrane proteins such as bacteriorhodopsin and Ca2+-ATPase (Alonso et al, 1982;Gomez-Fernandez et al, 1980).…”