High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules

Nature Communications
George R Heath, Simon Scheuring


Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecules underneath. This gives Angstrom spatial and microsecond temporal resolutions. In conjunction with HS-AFM imaging modes to precisely locate areas of interest, HS-AFM-HS measures simultaneously surface concentrations, diffusion coefficients and oligomer sizes of annexin-V on model membranes to decipher key kinetics allowing us to describe the entire annexin-V membrane-association and self-assembly process in great detail and quantitatively. This work displays how HS-AFM-HS can assess the dynamics of unlabeled bio-molecules over several orders of magnitude and separate the various dynamic components spatiotemporally.


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Methods Mentioned

fluorescence correlation spectroscopy
light microscopy
protein folding
electron microscopy

Related Concepts

Plasma Membrane
Staining and Labeling
Annexin A5
Microscopy, Atomic Force
Time-Lapse Imaging
Spatial Distribution
Spectrum Analysis

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