Abstracts
Ada Yonath Lecture:
Molecule-scale resolution and dynamics in fluorescence microscopy
Stefan W. Hell
Max Planck Institute for Multidisciplinary Sciences, Göttingen &
Max Planck Institute for Medical Research, Heidelberg
I will show how an in-depth description of the basic principles of diffraction-unlimited fluorescence microscopy has spawned MINFLUX [1-4], a recent superresolution method that
has reached the resolution of the size of a fluorophore molecule. Providing 1–3 nanometer resolution in fixed and living cells, as well as localization precisions in the Angström range,
MINFLUX and the related MINSTED concept [5,6] are being established for routine applications in the biomedical sciences [4]. Relying on fewer fluorescence photons than other
methods, these techniques are also poised to characterize dynamic processes at the single protein level, as already demonstrated by tracking sub(nanometer) details of the unhindered
stepping of the motor protein kinesin-1 on microtubules at up to physiological ATP concentrations [7].
[1] Balzarotti, F., Eilers, Y., Gwosch, K. C., Gynnå, A. H., Westphal, V., Stefani, F. D., Elf, J., Hell, S.W. Nanometer
resolution imaging and tracking of fluorescent molecules with minimal photon fluxes. Science 355, 606-612 (2017).
[2] Eilers, Y., Ta, H., Gwosch, K. C., Balzarotti, F., Hell, S. W. MINFLUX monitors rapid molecular jumps with superior
spatiotemporal resolution. PNAS 115, 6117-6122 (2018).
[3] Gwosch, K. C., Pape, J. K., Balzarotti, F., Hoess, P., Ellenberg, J., Ries, J., Hell, S. W. MINFLUX nanoscopy delivers
3D multicolor nanometer resolution in cells. Nat. Methods 17, 217–224 (2020).
[4] Schmidt, R., Weihs, T., Wurm, C. A., Jansen, I., Rehman, J., Sahl, S. J., Hell, S. W. (2021) MINFLUX nanometer-
scale 3D imaging and microsecond-range tracking on a common fluorescence microscope. Nat. Commun. 12:1478.
[5] Weber, M., Leutenegger, M., Stoldt, S., Jakobs, S., Mihaila, T. S., Butkevich, A. N., Hell, S. W. MINSTED
fluorescence localization and nanoscopy. Nat. Photon. 15, 361-366 (2021).
[6] Weber, M., von der Emde, H., Leutenegger, M., Gunkel, P., Sambandan, S., Khan, T. A., Keller-Findeisen, J., Cordes,
V. C., Hell, S.W. MINSTED nanoscopy enters the Ångström localization range. Nat. Biotechnol., 41, 569-576 (2023).
[7] Wolff, J.O., Scheiderer, L., Engehard, T., Engelhardt, J., Matthias, J., Hell, S.W.
MINFLUX dissects the unimpeded walking of kinesin-1, Science, 379, 1004-1010 (2023).