Phase Behavior and Nanoscale Structure of Phospholipid Membranes Incorporated with Acylated C14-Peptides

Abstract

The thermotropic phase behavior and lateral structure of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers containing an acylated peptide has been characterized by differential scanning calorimetry (DSC) on vesicles and atomic force microscopy (AFM) on mica-supported bilayers. The acylated peptide, which is a synthetic decapeptide N-terminally linked to a C14 acyl chain (C14-peptide), is incorporated into DPPC bilayers in amounts ranging from 0-20 mol %. The calorimetric scans of the two-component system demonstrate a distinct influence of the C14-peptide on the lipid bilayer thermodynamics. This is manifested as a concentration-dependent downshift of both the main phase transition and the pretransition. In addition, the main phase transition peak is significantly broadened, indicating phase coexistence. In the AFM imaging scans we found that the C14-peptide, when added to supported gel phase DPPC bilayers, inserts preferentially into preexisting defect regions and has a noticeable influence on the organization of the surrounding lipids. The presence of the C14-peptide gives rise to a laterally heterogeneous bilayer structure with coexisting lipid domains characterized by a 10 A height difference. The AFM images also show that the appearance of the ripple phase of the DPPC lipid bilayers is unaffected by the C14-peptide. The experimental results are supported by molecular dynamics simulations, which show that the C14-peptide has a disordering effect on the lipid acyl chains and causes a lateral expansion of the lipid bilayer. These effects are most pronounced for gel-like bilayer structures and support the observed downshift in the phase-transition temperature. Moreover, the molecular dynamics data indicate a tendency of a tryptophan residue in the peptide sequence to position itself in the bilayer headgroup region.

Tunable Membrane Binding of the Intrinsically Disordered Dehydrin Lti30, a Cold-Induced Plant Stress Protein

“…The biologically functional liquid crystalline phase is able to persist at lower temperatures. Similar shifts of the phase transition temperature (T m ) have been seen in the presence of other proteins or peptides (Cseh et al, 2000;Ivanova et al, 2003;Pedersen et al, 2005). Upon increasing the Lti30 to lipid fraction to a 1:30 molar ratio, the transition temperature drops even further (see Supplemental Figure 2 online).…”

Tracking peptide–membrane interactions: Insights from in situ coupled confocal-atomic force microscopy imaging of NAP-22 peptide insertion and assembly

“…2B), presumably because of an increase in lateral pressure of the surrounding lower l d domain. A similar reorganization was seen upon insertion of an acylated C14-peptide into pre-existing defect regions in membranes (Pedersen et al, 2005). While not myristoylated, other membrane-active peptides have also been shown to preferentially associate with the l d domain (Gandhavadi et al, 2002).…”

Cell‐penetrating peptide induces various deformations of lipid bilayer membrane: Inverted micelle, double bilayer, and transmembrane

“…In experiments of DPPC and peptide by Pedersen et al [27], peptide facilitates the formation of double or multiple bilayers. The peptide in their experiment is hydrophobic, but arginine-rich CPP is hydrophilic.…”