Quantitative characterization of biomolecular assemblies and interactions using atomic force microscopy

Abstract

Atomic force microscopy (AFM) has been applied in many biological investigations in the past 15 years. This review focuses on the application of AFM for quantitatively characterizing the structural and thermodynamic properties of protein–protein and protein–nucleic acid complexes. AFM can be used to determine the stoichiometries and association constants of multiprotein assemblies and to quantify changes in conformations of proteins and protein–nucleic acid complexes. In addition, AFM in solution permits the observation of the dynamic properties of biomolecular complexes and the measurement of intermolecular forces between biomolecules. Recent advances in cryogenic AFM, AFM on two-dimensional crystals, carbon nanotube probes, solution imaging, high-speed AFM, and manipulation capabilities enhance these applications by improving AFM resolution and the dynamic and operative capabilities of the AFM. These developments make AFM a powerful tool for investigating the biomolecular assemblies and interactions that govern gene regulation.