The Garcia-Manyes in interested in how mechanical forces affect biological entities, spanning from the single molecule to the whole cell. Below we highlight the main research areas of the research group.
1. Capturing the individual folding trajectories in a single protein
We are interested in studying the mechanical resistance of proteins that are in vivo continuously exposed to mechanical forces. Understanding the mechanisms of tissue elasticity requires comprehending how these proteins continuously and reversibly extend and recoil physiologically under the presence of a mechanical force. Paradigmatic examples of these proteins are muscle proteins, and in particular those present in cardiomyocytes, such as titin or myosin binding protein C. We are interested in studying the molecular mechanisms underpinning the reversible extension/collapse/folding dynamic cycle in these proteins. Finally, along the same lines, we are extending the single molecule mechanical studies to intercellular proteins that link the plasma membrane with the nuclear envelope as a putative way to swiftly transmit mechanical stimulus from the extracellular matrix to the cell nucleus.
2. Chemistry under force
A chemical reaction is classically activated by temperature, light or electricity. Force is an alternative, albeit much less explored, way to promote a chemical reaction. Using a combination of force clamp spectroscopy with molecular engineereing techniques we demonstrated that the SN2 reduction of an individual protein embedded disulfide bond is a force-activated process along a smooth energy landscape. We plan to experimentally reconstruct the full free-energy landscape of a chemical reaction under force. These novel experiments have opened a totally new way of inquiry in the chemistry field.
3. Cellular mechanics