Scattering imaging of biomolecules with metallic nanoparticles: localization precision, imaging speed, and multicolor imaging capability

Metallic nanoparticles, especially gold nanoparticles (AuNPs), have been widely used as bright optical probes for the observation and analysis of biomolecules. By continuously acquiring optical images of AuNPs bound to target molecules and analyzing their central coordinates, the behavior of a single biological molecule can be captured with high localization precision and high temporal resolution. This technique has been applied to a variety of biological studies, such as elucidating the operation mechanism of motor proteins that move forward at intervals as small as several nm, and the dynamics of lipid molecules that diffuse rapidly across biological membranes. In this review, I will focus on multicolor, high-speed, and high-precision optical imaging methods using metallic nanoparticles. These developments pave the way for a detailed understanding of the mechanisms of operation of tiny and complex biomolecules.