Unveiling Physics In Viruses: Breaking a Puzzle Box with a Hammer

Viruses are microscopic infectious agents that depend on host cells for replication. Their basic structure includes a viral genome, which encodes the genetic information necessary for replication, and a protective protein capsid, that exhibits remarkable physical properties essential for viral propagation. The viral capsid must balance stability to shield the viral genome with sufficient flexibility to transition into an unstable state that enables genome release into host cells.
This PhD thesis investigates the physical properties of viruses by drawing on principles from macroscopic materials science—such as stiffness, strength, and deformability. Atomic force microscopy (AFM) was used to probe the capsid physical properties of three distinct viruses: norovirus, human papillomavirus (HPV), and MS2 bacteriophage. Through nanoscale examination of their capsids, this research demonstrates close relationships between the structural and physical characteristics of these viruses. Subtle structural variations, such as those among different norovirus variants or due to glycan binding on HPV, could be detected through differences in viral physical properties. Even asymmetries within the viral capsids could be revealed from mechanical responses.
The findings offer valuable insights into the role of viral physical properties in regulating viral stability, infectivity, and interactions with host cells. Furthermore, this research suggests broader implications, such as the potential for virus identification based on unique physical signatures, and informs possible strategies for antiviral interventions.