EFFECT OF VESICLE SIZE ON THEIR INTERACTION WITH CLASS-A AMPHIPATHIC HELICAL PEPTIDES

Throughout the life span of a lipoprotein particle, the type and numbe r of exchangeable apolipoproteins on its surface varies with particle size, suggesting a role of surface curvature on the lipid-binding prop erties of these proteins. Peptides 18A, Ac-18A-NH2, Ac-18R-NH2, 37pA, and 37aA have been designed to investigate the lipid-binding propertie s of the amphipathic alpha-helix structural motif that appears to modu late the lipid-binding properties of the exchangeable plasma apolipopr oteins. We report here the results of a quantitative thermodynamic cha racterization of tile effects of modifying helix length and of varying both the location of charged residues about the polar face of tile pe ptides and vesicle size on the lipid affinity and depth of bilayer pen etration for model amphipathic alpha-helices. Partition coefficients, K-p, were determined by fluorescence spectroscopy, and binding enthalp ies, Delta H, by titration calorimetry. The results indicate that K-p values are on the order of 10(5), with similar Delta G degrees values for the interactions of the peptides with vesicles of various sizes. I t appears that a class A motif and increased alpha-helical content opt imize binding for 18-residue peptides. The interactions of the model p eptides with 20 nm SUV are enthalpically driven with small, negative e ntropy changes; however, interactions for larger vesicles are entropic ally driven, likely due to disordering of bilayer hydrocarbon chains T hermodynamic data indicate that 37pA and 37aA induce greater disorderi ng of bilayer hydrocarbon chains than Ac-18A-NH2. The results of this study suggest that the type of interaction, i.e., enthalpically or ent ropically driven, may be modulated by the lateral compressibility of t he bilayer membrane.