High-Speed Atomic Force Microscopy in Biological Systems

High-speed atomic force microscopy (HS-AFM) has emerged as a transformative tool for characterising the dynamic behaviour of biological specimens at nanometre spatial and millisecond temporal scales. By oscillating or raster-scanning a sharp probe over a hydrated sample, HS-AFM captures real-time conformational changes in single biomolecules, transient intermolecular interactions and large-scale morphological transitions in living cells. Advances in scanner design, small high-resonance cantilevers and refined feedback control have enabled routine imaging rates of tens of frames per second without compromising force sensitivity. Such developments permit direct observation of enzyme catalysis, protein assembly and membrane dynamics under near-physiological conditions. Moreover, innovations in multimodal operation—combining topography with mechanical and electrical mapping—and in data analysis, including machine-learning-based denoising, have broadened the scope of HS-AFM to address questions in mechanobiology, structural virology and biomaterials engineering. The technique’s capacity to bridge single-molecule biophysics with cellular physiology offers unique insights into the forces and motions that underpin fundamental life processes, while its growing compatibility with correlative optical and spectroscopic methods promises increasingly comprehensive views of complex biological systems.

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High-Speed Atomic Force Microscopy in Biological Systems publication trend

The graph below shows the total number of articles in high-speed atomic force microscopy in biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Atomic Force Microscopy (AFM): A technique that maps surface topography and mechanical properties by measuring forces between a sharp probe and sample.

High-Speed AFM (HS-AFM): A variant of AFM optimised for rapid imaging through small, high-resonance cantilevers and fast feedback loops, achieving millisecond-scale frame rates.

Cantilever: A microfabricated beam that holds the AFM tip; its deflection under force is monitored to derive surface features.

Tip-Sample Interaction: The force and displacement relationship between the probe tip and the biological specimen, determining resolution and contrast.

Spatial Resolution: The smallest lateral distance at which two distinct features can be distinguished, typically in the nanometre range for HS-AFM.

Temporal Resolution: The minimum time interval over which dynamic changes can be resolved, often in the millisecond domain for HS-AFM.

References

1. Unveiling the nanoscale architectures and dynamics of protein assembly with in situ atomic force microscopy. Aggregate (2024).
2. Atomic force microscopy in the characterization and clinical evaluation of neurological disorders: current and emerging technologies. Med-X (2024).
3. Long-tip high-speed atomic force microscopy for nanometer-scale imaging in live cells. Scientific Reports (2015).
4. An ultra-wide scanner for large-area high-speed atomic force microscopy with megapixel resolution. Scientific Reports (2021).
5. Faster high-speed atomic force microscopy for imaging of biomolecular processes. Review of Scientific Instruments (2021).
6. High-frequency multimodal atomic force microscopy. Beilstein Journal of Nanotechnology (2014).