High-Speed AFM and Applications to Biomolecular Systems

Abstract

Directly observing individual protein molecules in action at high spatiotemporal resolution has long been a holy grail for biological science. This is because we long have had to infer how proteins function from the static snapshots of their structures and dynamic behavior of optical makers attached to the molecules. This limitation has recently been removed to a large extent by the materialization of high-speed atomic force microscopy (HS-AFM). HS-AFM allows us to directly visualize the structure dynamics and dynamic processes of biological molecules in physiological solutions, at subsecond to sub-100-ms temporal resolution, without disturbing their function. In fact, dynamically acting molecules such as myosin V walking on an actin filament and bacteriorhodopsin in response to light are successfully visualized. In this review, we first describe theoretical considerations for the highest possible imaging rate of this new microscope, and then highlight recent imaging studies. Finally, the current limitation and future challenges to explore are described.

High-speed atomic force microscopy reveals structural dynamics of amyloid β 1–42 aggregates

“…In the present study, we used high-speed atomic force microscopy (HS-AFM) (40,41) to study the dynamics of Aβ assembly. We were able to visualize initial fibril nucleation and subsequent fibril elongation.…”

Extracting signal from noise: kinetic mechanisms from a Michaelis–Menten‐like expression for enzymatic fluctuations

“…For example, the peak value of n min for the packaging motor of φ29 is approximately 4.5, which is approximately equal to the sum of the two asymptotic limits, N L + N s = 1.6 AE 3.3 = 4.9. Recall that a controls the value of the local extremum of n min and its position along the substrate axis via Eqns (27,28). A peak that is comparable to the sum of the two asymptotic limits indicates a small, potentially zero value for a.…”

Applications of Atomic Force Microscopy in Exploring Drug Actions in Lymphoma-Targeted Therapy at the Nanoscale

“…Cell surfaces exposed to the pores are rigid, and therefore, we may obtain high-resolution images of the local areas on the cell surface. On the other hand, we can improve the AFM imaging mode; e.g., inspired by scanning ion conductance microscopy (SICM), we may develop non-contact AFM imaging mode [58]. At the noncontact mode, AFM tip does not contact the cell surface (avoiding the deformations of cell surface caused by AFM), and thus, it may improve the spatial resolution of imaging.…”