Interaction of Ordered Lipid Domain Boundaries and Amphipathic Peptides Regulates Probability of Pore Formation in Membranes

Abstract

Biological membranes include various lipids. A heterogeneity of lipid composition can lead to phase separation resulting in the formation of ordered lipid domains, which differ in lipid composition from the other (disordered) part of the membrane. Membrane deformations, which occur at the domain boundary, can affect the lateral distribution of various membrane inclusions. In this paper, in the framework of theory of elasticity of lipid membranes, the influence of the boundaries of lipid domains on the lateral distribution of amphipathic peptides adsorbed on the membrane is considered. Such peptides can cause the formation of through pores. We showed that with an increase in the concentration of amphipathic peptides on the membrane, they first line up near the boundary of the domain parallel to it, thus losing the ability to induce pore formation. Then, as the domain boundary is completely occupied, new peptides stand parallel to the line of peptides that are already at the boundary, at a distance of about 5 nm from the boundary. In this configuration, the probability of formation of through pores in the membrane is increased. Besides, it is shown that the spontaneous curvature of monolayers of the ordered domain and disordered membrane determines the energy of incorporation of peptides into the membrane and their distribution between the phases. However, the spontaneous curvature scarcely influences the interaction of amphipathic peptides with the boundary of the ordered domain.