Applied Mechanics Colloquia Applied Physics Colloquia

High-Speed Atomic Force Microscopy (HS-AFM) Uncovers a Rare and Transient Pentameric State in the Sensory Ion Channel TRPV3

Simon Scheuring (Cornell University)

Friday, Dec 8, 2023
11:00 am to 12:00 pm | Pierce Hall, 209 | Remote option

High-speed atomic force microscopy (HS-AFM) is a powerful technique that provides dynamic movies of biomolecules at work. First, I will briefly review our recent developments to break temporal limitations to characterize molecular dynamics by developing HS-AFM line scanning (HS-AFM-LS) and HS-AFM height spectroscopy (HS-AFM-HS) [1], and resolution limitations by developing Localization AFM (LAFM) [2]. Then, I will detail how we used HS-AFM to analyze membrane-embedded Piezo1 [3] and TRPV3 [4] sensory ion channels at the single-molecule level, and discovered a previously unobserved, transient and reversible pentameric state in TRPV3 [4].



[1] Heath et al., Nature Communications, 2018, 9(1):4983, High-Speed AFM Height Spectroscopy (HS-AFM-HS): Microsecond dynamics of unlabeled biomolecules.

[2] Heath et al., Nature, 2021, 594(7863):385–390, doi:10.1038/s41586-021-03551-x, Localization Atomic Force Microscopy.

[3] Lin et al., Nature, 2019, 573(7773):230–234, doi.10.1038/s41586-019-1499-2, Force-induced conformational changes in Piezo1.

[4] Lansky et al., Nature, 2023, 621(7977), 206–214, doi:10.1038/s41586-023-06470-1, A pentameric TRPV3 channel with a dilated pore.

Speaker Bio

Simon Scheuring is a trained biologist (Biozentrum, University of Basel, Switzerland). During his MSc and PhD, he learned electron microscopy (EM) and atomic force microscopy (AFM) for the structure determination of membrane proteins such as aquaporins and sugar transporters (Engel laboratory). During his postdoc and as research assistant (Rigaud laboratory, INSERM / Institut Curie, Paris, France), he learned membrane physical chemistry and developed AFM for the study of native membranes and ventured into setting up his lab as a junior research director at the Institut Curie. Promoted to senior research director, he built a larger independent laboratory in Marseille (INSERM / Aix-Marseille Université, France). In 2017, he moved to Weill Cornell Medicine, where he got appointed as Professor of Physiology and Biophysics in Anesthesiology (WCM, New York, USA). Simon Scheuring’s laboratory develops and applies AFM-technologies for the study of membrane phenomena, such as membrane protein structure, assembly, diffusion and conformational dynamics. Over the past years, his laboratory has been instrumental in the development and application of High-Speed AFM (HS-AFM), unique for the analysis of dynamics of unlabeled single molecules, bridging structure and function. To enhance HS-AFM for biological applications, his laboratory developed environmental control, i.e., slow, and fast buffer exchange, temperature, and force control. Further developments covered novel AFM-modalities, (i) integrating optical microscopy and HS-AFM, (ii) developing high-speed force spectroscopy (HS-FS) and (iii) high frequency microrheology (HF-µR). Most recently, Simon Scheuring’s laboratory worked on breaking current speed and resolution limitations of AFM. Developing HS-AFM line scanning (HS-AFM-LS) and HS-AFM height spectroscopy (HS-AFM-HS), the group probes molecular dynamics at millisecond and microsecond temporal resolution. By developing Localization Atomic Force Microscopy (LAFM), a super-resolution AFM method, Simon Scheuring’s lab can extract quasi-atomic structural details from single molecule AFM data. Taking advantage of these possibilities, Simon Scheuring made significant contributions in the membrane trafficking, and the channels and transporters fields.

Simon Scheuring authored >100 research articles, among them publications in Cell, Science, Nature, Nature Nanotechnology, Nature Cell Biology, Nature Methods, Nature Physics, Nature Communications, PNAS, EMBO J, etc, >30 review articles and >15 didactic writings, such as book and methods chapters. He has been awarded an INSERM Avenir (2005), the médaille de la Ville de Paris (2007), a European Research Council (ERC) grant (2012), the Grand Prix Robert Debré (2013), the NIH Director's Pioneer Award (2019), and the WM Keck Foundation Medical Research Award (2022).


AP/MSME Colloquium Series


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