Modeling of the Interaction of Viral Fusion Peptides with the Domains of Liquid-Ordered Phase in a Lipid Membrane

Abstract

Membrane microdomains enriched with sphingomyelin and cholesterol, the so-called rafts, are thicker than the surrounding membrane. To smooth the thickness mismatch, the membrane is deformed, which leads to the formation of a complex asymmetric structure of the raft boundary. The rafts are of great importance in the process of viral infection of the cell: for example, in recent experiments it has been shown that the fusion peptide of human immunodeficiency virus (HIV) tends to be predominantly inserted at the raft boundary, and the effectiveness of the fusion was low in the absence of the rafts. It has been noticed in these studies that such preferential distribution of fusion peptides was not found in the case of influenza virus. In the present paper, we modeled the interaction of fusion peptides with rafts by the methods of elasticity theory of lipid membranes. We have shown that the boundary of the liquid-ordered domains can act as an attractor for the fusion peptides: peptides distribute to the raft boundary and play the role of line-active membrane components. Our model enables to explain the difference of the behavior of different fusion peptides in the presence of rafts in the above mentioned example of the experimental data by different geometry of their insertion into the lipid monolayer. Our results show the fundamental mechanisms by which the geometry of fusion peptide insertion affects their distribution in the lipid membrane.