Disassembly ofVirus-Like Particles and the StabilizingRole of the Nucleic Acid Cargo

In many simple viruses and virus-like particles, the protein capsid self-assembles around a nucleic-acid genome. Although the assembly process has been studied in detail, relatively little is known about how the capsid disassembles, a potentially important step for infection (in viruses) or cargo delivery (in virus-like particles). We investigate capsid disassembly using a coarse-grained molecular dynamics model of a <i>T</i> = 1 dodecahedral capsid and an RNA-like polymer. We alter the interactions between the subunits of the capsid as well as the ionic strength of the solution to induce partial or complete disassembly of self-assembled particles. We find that disassembly follows nucleation-and-growth kinetics, where the nucleation barrier is related to the interaction strengths as well as to the conformation of the polymer. In particular, we find that polymer segments that interact with adjacent subunits reinforce the subunit–subunit contacts. These results have implications for the design of virus-like particles for applications such as drug delivery. A cargo designed with reinforcement in mind might be used to control the stability of such particles and mediate disassembly.