Julio M. Fernandez

Protein folding and chemistry under force. 

I created a new field of science: single protein force spectroscopy.  My goal was to understand the folding dynamics and chemistry of single proteins placed under a stretching force, of common occurrence in biology, yet poorly understood.  My work initially focused on developing molecular biological tools to engineer proteins that provided mechanical fingerprints and anchors with which to identify them against the vast amount of background mechanical noise which always accompanies single protein recordings.  Over the years I applied these novel techniques to understand the folding dynamics of the giant muscle protein titin and its role in muscle physiology.  I also did similar protein folding studies on other proteins of interest.   The most unexpected discoveries of my studies over the years were that single proteins readily fold against a pulling force delivering mechanical work at a very high rate (thousands of zeptowatts), and that chemical reactions in proteins are force-dependent. These findings have vast implications for understanding how muscle contraction works, but also as general mechanisms for the regulation of protein dynamics throughout biological systems.

1. Fernandez, J.M. and Li, H. B. (2004), Force-clamp spectroscopy monitors the folding trajectory of a single protein, Science, 303: 1674-1678.
2. Rivas-Pardo, Jaime Andrés, Edward C. Eckels, Ionel Popa, Pallav Kosuri, Wolfgang A. Linke, and Julio M. Fernández. (2016), Work Done by Titin Protein Folding Assists Muscle Contraction, Cell Reports 14: 1339–47.
3. Edward C. Eckels, Shubhasis Haldar, Rafael Tapia-Rojo, Jaime Andres Rivas-Pardo, and Julio M. Fernandez. (2019) The Mechanical Power of Titin Folding. Cell Reports, 27: 1836-1847.
4. Wiita, A.P., Ainavarapu, S.R.K., Huang, H.H. and Julio M. Fernandez (2006) Force-dependent chemical  kinetics of disulfide bond reduction observed with single molecule techniques. Proc Natl Acad Sci USA. 103:7222-7.
5. Wiita, A.P., Perez-Jimenez, R., Walther, K.A., Gräter, F. Berne, B.J., Holmgren, A., Sanchez-Ruiz, J.M., and Fernandez, J.M. (2007) Probing the chemistry of thioredoxin catalysis with force. Nature 450:124-7.