The application of atomic force microscopy for viruses and protein shells: Imaging and spectroscopy.

Abstract

Atomic force microscopy (AFM) probes surface-adsorbed samples at the nanoscale by using a sharp stylus of nanometric size located at the end of a micro-cantilever. This technique can also work in a liquid environment and offers unique possibilities to study individual protein assemblies, such as viruses, under conditions that resemble their natural liquid milieu. Here, I show how AFM can be used to explore the topography of viruses and protein cages, including that of structures lacking a well-defined symmetry. AFM is not limited for imaging and allows the manipulation of individual viruses with force spectroscopy approaches, such as single indentation and mechanical fatigue assays. These pushing experiments deform the protein cages to obtain their mechanical information and can be used to monitor the structural changes induced by maturation or the exposure to different biochemical environments, such as pH variation. We discuss how studying capsid rupture and self-healing events offers insight into virus uncoating pathways. On the other hand, pulling tests can provide information about the virus-host interaction established between the viral fibers and the cell membrane.