Structural transitions and energy landscape for Cowpea Chlorotic Mottle Virus capsid mechanics from nanomanipulation in vitro and in silico

TL;DR

This study combines experimental and computational approaches to explore the mechanical behavior and structural transitions of Cowpea Chlorotic Mottle Virus capsids under deformation, revealing their dynamic and reversible properties.

Contribution

It provides new insights into the energy landscape and mechanical transitions of virus capsids through integrated nanomanipulation and modeling, highlighting their dynamic physical properties.

Findings

Capsids transition to collapsed state without local structural change.

Large deformations involve significant enthalpy and entropy changes.

Capsid elasticity is governed by coupled out-of-plane and in-plane modes.

Abstract

Physical properties of capsids of plant and animal viruses are important factors in capsid self-assembly, survival of viruses in the extracellular environment, and their cell infectivity. Virus shells can have applications as nanocontainers and delivery vehicles in biotechnology and medicine. Combined AFM experiments and computational modeling on sub-second timescales of the indentation nanomechanics of Cowpea Chlorotic Mottle Virus (CCMV) capsid show that the capsid's physical properties are dynamic and local characteristics of the structure, which depend on the magnitude and geometry of mechanical input. Surprisingly, under large deformations the CCMV capsid transitions to the collapsed state without substantial local structural alterations. The enthalpy change in this deformation state dH = 11.5 - 12.8 MJ/mol is mostly due to large-amplitude out-of-plane excitations, which contribute to the capsid bending, and the entropy change TdS = 5.1 - 5.8 MJ/mol is mostly due to coherent in-plane rearrangements of protein chains, which result in the capsid stiffening. Dynamic coupling of these modes defines the extent of elasticity and reversibility of capsid mechanical deformation. This emerging picture illuminates how unique physico-chemical properties of protein nanoshells help define their structure and morphology, and determine their viruses' biological function.