Size and mechanical stability of norovirus capsids depend on pH: a nanoindentation study

Abstract

Norovirus-like particles were imaged using atomic force microscopy. The mechanical stability of the virus-like particles (VLPs) was probed by nanoindentation at pH values ranging from 2 to 10. This range includes pH values of the natural environment during the life cycle of noroviruses. The resistance of VLPs to indentation was constant at acidic and neutral pH. The Young's modulus was of the order of 30 MPa. At basic pH the compliance of the capsid increased along with an increase in diameter. This specific pH-dependent mechanical response of the capsid may be related to mechanisms controlling uptake and release of the RNA during infection. Consecutive indentations with pressures ≤ 300 bar demonstrated the ability of the capsids to fully recover from deformations comparable with the size of the capsid. The capsids can be viewed as nanocontainers with an inbuilt self-repair mechanism. At pH 10 the capsids lost their stability and were irreversibly destroyed after one single indentation.

Mechanical elasticity as a physical signature of conformational dynamics in a virus particle

“…Developments in atomic force microscopy (AFM) (7,8) have recently led to the experimental investigation of the mechanical properties of single virus particles (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The mechanical elasticity of virions and capsids can be probed using the approach pioneered in ref.…”

Force Microscopy – A Tool to Elucidate the Relationship Between Nanomechanics and Function in Viruses

“…The capsids observed irreversible deformation for indentation forces close to 1 nN. Our own work on Norovirus (NV) virus-like particles showed a relationship between stiffness and size on one hand and the pH value on the other hand (Cuellar, et al, 2010). It was concluded that these changes are related to a modulation of non-covalent interactions among the capsomers by the pH.…”

“…The exceptional mechanical stability found for the HSV-1 virus might be a key factor for the survival during transport over long distances of the axonal cytoplasm where is exposed to mechanical stresses by molecular motors before it reaches its final point for cargo release (Liashkovich, et al, 2008). The reported mechanical stability and self-healing mechanism in Norovirus capsids (Cuellar, et al, 2010) with regard to drastic changes in pH may be an essential requirement for infection. To succeed as a pathogen the capsid has to survive the highly acidic pH in the stomach and become infectious under the weakly basic conditions within the ileum.…”

“…Theoretically it should be possible to visualize the hexameric and pentameric arrangements of proteins within capsomers or the localization of spike proteins at the surface. Nevertheless, for viruses which have crowded proteins coronas with only narrow molecular canyons, like Norovirus and Cowpea Chlorotic Mottle virus, high resolution images at the surface are limited by the geometrical constraints of the tip (Cuellar, et al, 2010. In these cases, with typical commercial Silicon Nitride tips with a radius of about 15 nm the viruses appear as hemispherical caps as shown in figure 3.…”

“…However, it has to be taken into account that adhesion forces if strong enough could lead to flattening of VLP´s. This may lead to a subsequent underestimation of the diameter of the virus (Cuellar, et al, 2010). In the context of imaging it is thus advisable to study the affinity of the viruses to the surface, because if the attachment is too weak imaging might induce detachment.…”