Biomolecular Nano-Dynamics

At the Nano Dynamics Lab, we are fascinated by the molecular dynamics found in biomolecules, and we strive to investigate them experimentally at the single-molecule level using cutting-edge nanopore & smFRET techniques.

Proteins are the molecular makers in our body. They perform all vital cellular functions to maintain life as we know it: cell growth & division, genome replication & repair, energy harvesting & conversion, self-defence & attack, environmental sensing & reaction to it, etc. etc. To do this all, proteins adopt different 3D conformations and change their interaction partners dynamically. However, these essential molecular dynamics are challenging to observe and dissect experimentally, because they usually happen unsynchronized in a large molecular ensemble.

To tackle this, in the NanoDynamicsLab, we use & develop innovative single-molecule techniques to gain quantitative insight into biomolecular dynamics, in order to understand the molecular basis of protein function and also malfunction leading to disease. In particular, we are fascinated by how functional dynamics arise from specific structural elements (protein domains, or even single atoms) in the context of diverse energy sources, including thermal and chemical energy, light, ion gradients etc. And we aim to understand and alter such nanoscale processes in a controlled way.

Selected Publications

Fuentenebro-Navas, D., Steens, J. A., de Lannoy, C., Noordijk, B., de Ridder, D., Staals, R. H. J., & Schmid, S. (2023). Nanopores reveal the stoichiometry of single oligo-adenylates produced by type III CRISPR-Cas [Posted-content]. In Biorxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2023.08.18.553839

URLs

Wen, C., Bertosin, E., Shi, X., Dekker, C., & Schmid, S. (2023). Orientation-Locked DNA Origami for Stable Trapping of Small Proteins in the Nanopore Electro-Osmotic Trap. Nano Letters, 23(3), 788–794. https://doi.org/10.1021/acs.nanolett.2c03569

URLs

Götz, M., Barth, A., Bohr, S. S.-R., Börner, R., Chen, J., Cordes, T., Erie, D. A., Gebhardt, C., Hadzic, M. C. A. S., Hamilton, G. L., Hatzakis, N. S., Hugel, T., Kisley, L., Lamb, D. C., de Lannoy, C., Mahn, C., Dunukara, D., de Ridder, D., Sanabria, H., et al. (2022). A blind benchmark of analysis tools to infer kinetic rate constants from single-molecule FRET trajectories. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-33023-3

URLs

Schmid, S., Stömmer, P., Dietz, H., & Dekker, C. (2021). Nanopore electro-osmotic trap for the label-free study of single proteins and their conformations. Nature Nanotechnology, 16(11), 1244–1250. https://doi.org/10.1038/s41565-021-00958-5

URLs

Schmid, S., & Hugel, T. (2020). Controlling protein function by fine-tuning conformational flexibility. eLife, 9, 1–14. https://doi.org/10.7554/elife.57180

URLs