Osmotically-induced rupture of viral capsids

TL;DR

This paper presents a thermodynamic and elastic model to analyze how osmotic shocks caused by salt concentration changes can induce rupture in viral capsids, highlighting the physical mechanisms and stability conditions involved.

Contribution

It introduces a combined thermodynamic and elastic framework to predict viral capsid stability under osmotic stress, incorporating ion effects, membrane elasticity, and pore formation mechanisms.

Findings

Capsids can rupture or remain stable depending on initial conditions and surface strength.

The model captures key physical mechanisms like volume exclusion, entropy, and elastic costs.

Stability depends on the extent of ionic dilution and capsid properties.

Abstract

A simple model is proposed aimed to investigate how the amount of dissociated ions influences the mechanical stability of viral capsids. After an osmotic and mechanical equilibrium is established with the outer solution, a non-adiabatic change in salt concentration at the external environment is considered, which results in a significant solvent inflow across the capsid surface, eventually leading to its rupture. The key assumption behind such an osmotic shock mechanism is that solvent flow takes place at timescales much shorter than the ones typical of ionic diffusion. In order to theoretically describe this effect, we herein propose a thermodynamic model based on the traditional Flory theory. The proposed approach is further combined with a continuum Hookian elastic model of surface stretching and pore-opening along the lines of a Classical Nucleation Theory (CNT), allowing us to establish the conditions under which capsid mechanical instability takes place. Despite its non-local character, the proposed model is able to capture most of the relevant physical mechanisms controlling capsid stability, namely the volume exclusion and entropy of mixing effects among the densely-packed components, the elastic cost for capsid stretching and further pore opening, the Donnan equilibrium across the interface, as well as the large entropy loss resulting from folding the viral genome into close-packed configurations inside the capsid. It is shown that, depending on the particular combination of initial condition and capsid surface strength, the capsid can either become unstable after removal of a prescribed amount of external salt, or be fully stable against osmotic shock, regardless of the amount of ionic dilution.