# Using atomic force microscopy for physical virology: touching and manipulating single virus particles

## TL;DR

This paper explores how atomic force microscopy can be used to study and manipulate individual virus particles, including imaging, measuring their mechanical properties, and observing virus assembly and disassembly.

## Contribution

The paper introduces novel applications of AFM for physical virology, including biomechanical analysis and real-time observation of virus processes.

## Key findings

- AFM can image individual viruses in liquid with high resolution and manipulate single particles.
- Mechanical fatigue protocols reveal the mechanical properties of TMV and viral coat proteins.
- AFM can trigger genome release in MVM and move viruses across surfaces to measure adhesion strength.

## Abstract

Atomic force microscopy (AFM) employs a nanometer-scale tip mounted on a microcantilever to scan surfaces where virus particles have been captured. Beyond generating high-resolution images of individual virions in liquid, AFM offers unique capabilities: manipulation of single particles, investigation of their biomechanical properties, and real-time observation of assembly and disassembly processes, including genome release. This chapter begins by outlining fundamental aspects of virus adsorption and imaging, highlighting, among other factors, the influence of tip-convolution artifacts. These principles are applied to reveal the adsorption behavior of the TGEV coronavirus on surfaces. Subsequent sections detail approaches for probing TMV’s mechanical properties through single-indentation experiments and mechanical fatigue protocols. In this section, the mechanical fatigue approach is also discussed when used on 2D arrays of viral coat proteins. The review also discusses how these mechanical techniques can trigger genome release in minute virus of mice (MVM), a process that can alternatively be induced by temperature, as happens in bacteriophage T7. Finally, the chapter illustrates how AFM can serve as a nanomanipulation tool to move individual viruses across surfaces and estimate their adhesion strength.