Force is a ubiquitous modulator of protein function in biology. We have developed single molecule AFM techniques to study how mechanical forces affect the dynamics and chemistry of proteins. Using molecular biological techniques, we engineer tandem modular proteins that are made of identical repeats of a protein of interest. These polyproteins act as handles for atomic force microscopes, without the need for linkers or special attachment chemistry. When such polyproteins are extended by an AFM, their force properties are unique mechanical fingerprints that unambiguously distinguish them from the more frequent non-specific events that plague single molecule studies. We combine polyprotein engineering together with active force-clamp AFM techniques. With this approach, the length of an extending polyprotein is measured while the pulling force is actively kept constant by negative feedback control. We study the force dependency of protein folding, unfolding and chemical reactions. From the force dependence, we extract features of the transition state of these reactions that reveal underlying molecular mechanisms.

News update (July 2009): Raul Perez-Jimenez's study on the diversity of chemical mechanisms in thioredoxin enzymes has been published in Nature Structural & Molecular Biology. Read it here.

Also check our three articles, just published by PNAS (1, 2, 3), examining the collapsed states formed by proteins after a mechanical extension. Our studies have implications for understanding protein folding and Huntington's disease.

News update (June 2009): Sergi Garcia-Manyes' recent paper in Nature Chemistry is featured in a News & Views article in the journal's June issue.

Together with Mike Sheetz' group we published in Science a study of the mechanical properties of the signaling protein talin. This study was featured in a Perspectives article in the journal's January issue.