Atomic force microscopy observation and characterization of single virions and virus-like particles by nano-indentation

•Review of the most recent studies in Mechanical Virology, using AFM nano-indentation.•Mechanics of structural capsid changes during maturation.•Uncoating mechanisms in relation to environmental factors and virus-host interactions.•Capsid (de-)stabilization due to genome-capsid interactions and environmental conditions.

Structure and function of viruses are intimately related, and one of the goals in virology is to elucidate the mechanisms behind this relation. A variety of research endeavours is focused on studying these mechanisms and a relatively new technique in this field is Atomic Force Microscopy (AFM). Using AFM virions and virus-like particles can be imaged and manipulated at the single particle level. Here we review recent AFM nano-indentations studies unveiling for instance the mechanics of capsid-genome interactions, morphological changes that drive viral maturation, capsid stabilizing factors and viral uncoating. We show that in an increasing amount of literature a clear link between mechanics and infectivity is observed, which not only provides us with new fundamental insights into virology, but also provides ways to improve virus-like particles for applications in nanomedicine and nanotechnology.

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