Professor Sergi Garcia-Manyes

Research summary

The main focus of my research is to understand the molecular mechanisms that confer mechanical stability to well-defined systems, which is a major challenge in modern physics, chemistry and biology.

For example, while cell mechanics is known to play a decisive role in determining cell shape and also in endo- and exocytosis, the chemical origin of the membrane mechanical resistance remains largely unknown. Using force-spectroscopy AFM, we can decipher the molecular determinants that provide lipid bilayers with unexpectedly high mechanical stabilities.

Most importantly, we investigate the molecular mechanisms by which proteins equilibrate under the effect of a constant stretching force. We use the newly developed single molecule force-clamp spectroscopy technique to elucidate, with exquisite sub-Ǻngström sensitivity, the dynamics of proteins as they unfold, collapse and refold in response to a mechanical force. I am most interested in examining the conformational dynamics of a single refolding protein during its individual folding trajectory from highly extended states.

Finally, we use our force-clamp assay to examine, at the single bond level, how force affects the chemical mechanisms of disulfide bond reduction in proteins exposed to mechanical forces. Within a multidisciplinary approach, we conduct a series of innovative experiments to directly probe the effect of force on the function of an individual folding polypeptide and also the mechanisms by which mechanical forces modulate chemical reactions. The force spectroscopy data is providing a new view that will help guide the development of theories on the dynamics of folding and ab-initio studies of a chemical reaction placed under a stretching force, of common occurrence in nature

Keywords

Elasticity, Protein Folding, Reaction Mechanisms, Surfaces, Transition States, Bionanoscience, Nano-Bio Systems, Proteins, Scanning-Probe Microscopies, Biomolecules

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