Saddle-curvature instability of lipid bilayer induced by amphipathic peptides: a molecular model.

Amphipathic peptides that partition into lipid bilayers affect the curvature elastic properties oftheir host. Some of these peptides are able to shift the Gaussian modulus to positive values, thustriggering an instability with respect to the formation of saddle curvatures. To characterize thegeneric aspects of the underlying mechanism, we employ a molecular lipid model that accounts forthe interfacial tension between the polar and apolar regions of the membrane, for interactions betweenthe lipid headgroups, and for the energy to stretch or compress the hydrocarbon chains. Peptidesare modeled as cylinders that partition into the host membrane in a parallel orientation where theydiminish the space available to the lipid headgroups and chains. The penetration depth into themembrane is determined by the angular size of the peptide’s hydrophilic region. We demonstratethat only peptides with a small angular size of their hydrophilic region have an intrinsic tendencyto render the Gaussian modulus more positive, and we identify conditions at which the Gaussianmodulus adopts a positive sign upon increasing the peptide concentration. Our model allows usto also incorporate electrostatic interactions between cationic peptides and anionic lipids on thelevel of the linear Debye-Huckel model. We show that electrostatic interactions tend to shift the Gaussian modulus toward more positive values. Steric and electrostatic lipid-peptide interactionsjointly decrease the effective interaction strength in the headgroup region of the host membranethus suggesting a generic mechanisms of how certain amphipathic peptides are able to induce theformation of saddle curvatures.