Virus Assembly on a Membrane is Facilitated by Membrane Microdomains

TL;DR

This study uses molecular dynamics simulations to explore how membrane microdomains, like lipid rafts, facilitate virus assembly by reducing barriers and promoting subunit association on fluctuating lipid membranes.

Contribution

It reveals mechanisms by which membrane microdomains enhance virus assembly, including a novel pathway not predicted by equilibrium theories.

Findings

Membrane microdomains reduce assembly barriers.

Assembly depends on multiple dynamic timescales.

Microdomains can promote or inhibit assembly depending on conditions.

Abstract

For many viruses assembly and budding occur simultaneously during virion formation. Understanding the mechanisms underlying this process could promote biomedical efforts to block viral propagation and enable use of capsids in nanomaterials applications. To this end, we have performed molecular dynamics simulations on a coarse-grained model that describes virus assembly on a fluctuating lipid membrane. Our simulations show that the membrane can promote association of adsorbed subunits through dimensional reduction, but also can introduce barriers that inhibit complete assembly. We find several mechanisms, including one not anticipated by equilibrium theories, by which membrane microdomains, such as lipid rafts, can enhance assembly by reducing these barriers. We show how this predicted mechanism can be experimentally tested. Furthermore, the simulations demonstrate that assembly and budding depend crucially on the system dynamics via multiple timescales related to membrane deformation, protein diffusion, association, and adsorption onto the membrane.