Mechanical control of the height distribution of adsorbed viral capsids

The height of viral particles adsorbed on solid substrates is governed by the equilibrium between adhesion energy and capsid elasticity. While the resulting height distribution has been proposed as a noninvasive proxy for viral stiffness, the physical origin of its broadening is unknown. In this work, we combine atomic force microscopy (AFM) topography measurements of adenoassociated virus (AAV8) and Hepatitis B virus (HBV) with a theoretical shell-deformation model to identify the determinants of height dispersion. By modeling the viral shell as an elastic body under adhesive load, we evaluate the relative contributions of thermal fluctuations and mechanical heterogeneity to the observed height dispersion. We demonstrate that thermal noise is insufficient to explain the width of the distribution. Instead, the data support a model where the dispersion in height arises from the intrinsic variability of capsid stiffness. This variability is associated to the surface inhomogeneity of identical capsids. Our results validate that, when this inhomogeneity is accounted for, the height distribution of adsorbed particles provides a quantitative measure of viral mechanics without the need for individual nanoindentation.