Ph.D., Univ. of Chile, Santiago, 1987
Post-doctorate, Univ. of Pennsylvania, 1987-89
Post-doctorate, Mayo Clinic, Rochester, 1989-94
Assistant Professor at the University of Chile, 1995-97
Associate Professor, Centro de Estudios Cientificos de Santiago, 1995-97
About the Lab
Our lab is interested in the mechanism by which proteins respond to mechanical forces. A large fraction of the proteins have structural and thus also mechanical functions. Examples include muscle proteins (e.g. titin), cytoskeletal proteins (e.g. spectrin) and proteins of the extracellular matrix (e.g. fibronectin). However, not much is known how single proteins respond to mechanical forces. Do they behave as simple springs or do they display more complex features? Do they share common set of design principles and mechanical fingerprints?
We are currently studying the mechanical properties of elastin (an abundant component of connective tissue), polycystin-1 (a cell membrane receptor found mainly in kidney tubules) and projectin and twitchin (titin-like protein found in Drosophila and C. elegans). We hypothesize that these proteins function as a mechanical sensors that regulates several processes, including cell growth and tissue morphogenesis. We are testing this hypothesis by directly measuring their mechanical properties using novel Atomic Force Microscopy (AFM) techniques that are capable of tracking forced-induced conformational changes in single molecules.
Oberhauser, A.F. and Fernandez, JM. (1996). A fusion pore phenotype in mast cells of the ruby-eye mouse. Proc Natl Acad Sci. 93:14349-14354.
Oberhauser, A.F., Marszalek, P.E., Erickson, H.P., and Fernandez, J.M. (1998). The molecular elasticity of tenascin, an extracellular matrix protein. Nature. 393:181-185.
Oberhauser, A.F., Hansma, P.K., Carrion-Vazquez, M., and Fernandez, J.M. (2001). Stepwise unfolding of titin under force-clamp AFM. Proc Natl Acad Sci. 98:468-472.
Qian, F., Wei, W., Germino, G.G., and Oberhauser, A.F. (2005). The Nanomechanics of Polycystin-1 extracellular region. J Biol Chem. 280(49):40723-40730.
Oberhauser, A.F., Badilla-Fernandez, C., Carrion-Vazquez, M., and Fernandez, J.M. (2002). The mechanical hierarchies of fibronectin observed with single molecule AFM. J Mol Biol. 319(2):433-447.
Bullard, B., Benes., V., Garcia, T., Leake, M., Linke, W., and Oberhauser, A.F. (2006). The Molecular Elasticity of the Insect Flight Muscle Proteins Projectin and Kettin. Proc Natl Acad Sci. 103(12):4451-4456.
Miller, E., Garcia, T., Hultgren, S., & Oberhauser, A. (2006). The Nanomechanics of E. coli Pili. Biophys J. 91(10):3848-3856.
Oberhauser AF, Carrin-Vazquez M. (2008). Mechanical biochemistry of proteins one molecule at a time. J Biol Chem. Mar 14;283(11):6617-6621.
Greene, D.N., Garcia T., Sutton, RB, Gernert K. M., Benian, G. M., & Oberhauser AF. (2008). Single-molecule force spectroscopy reveals a stepwise unfolding of C. elegans giant protein kinase domains. Biophys J. 95(3):1360-1370.
Oberhauser AF and Braun W. (2008). Mechanical Stability and Differentially Conserved Physical-chemical Properties of Titin Ig-domains. Proteins. Sep 25;75(3):706-718.
Fuson, K., Ma, L., Sutton, RB & Oberhauser AF. (2009). The C2 domains of human Synaptotagmin 1 have distinct mechanical properties. Biophys J. 96(3): 1083-1090.
Ma L, Xu M, Forman JR, Clarke J. & Oberhauser A.F. (2009). Naturally occurring mutations alter the stability of polycystin-1 PKD domains. J Biol Chem. 4(47): 32942-32949.