Our group studies how biological systems work at the nanoscale, and the physical laws that govern their behavior. We are particularly interested in the weak, non-covalent interactions between and within biological molecules (e.g. base-pairing in nucleic acids, receptor-ligand bonding, protein folding, etc.), and the coupling of these interactions to mechanical force. To investigate these issues, we develop and apply novel techniques in single-molecule manipulation, detection, and analysis, including optical tweezers methods and high-resolution optical detection.
DNA NANOSWITCHES: A QUANTITATIVE PLATFORM FOR GEL-BASED BIOMOLECULAR INTERACTION ANALYSIS
We’ve developed a nanoscale experimental platform that enables kinetic and equilibrium measurements of a wide range of molecular interactions using a gel electrophoresis readout. Programmable, self-assembled DNA nanoswitches serve both as templates for positioning molecules, and as sensitive, quantitative reporters of molecular association and dissociation. (Artwork: Mark Daws)
NANOENGINEERING FUNCTIONAL SINGLE-MOLECULE TOOLS WITH DNA SELF-ASSEMBLY
We are engineering nanoscale tools for studying biomolecular interactions with DNA self-assembly. For example, we have developed a novel DNA mechanical switch that changes states under force to enable new studies in single-molecule kinetics.
SINGLE-MOLECULE CENTRIFUGATION: A NEW APPROACH FOR MASSIVELY-PARALLEL SINGLE-MOLECULE MANIPULATION
We are developing a new approach for performing massively parallel single-molecule force measurements using centrifugal force. This is accomplished with a new instrument that we call the Centrifuge Force Microscope. (Photo credit: John Chervinsky)
MECHANOENZYMATIC CLEAVAGE OF THE ULTRALARGE VASCULAR PROTEIN VON WILLEBRAND FACTOR
Using techniques in single-molecule manipulation, we have illuminated a fundamental feedback mechanism that the body uses to regulate the clotting of blood. Small tensile forces, such as those experienced in the circulation, can unfold the von Willebrand factor A2 domain, enabling its cleavage by the ADAMTS13 enzyme. This, in turn varies the body’s hemostatic potential. (Photo credit: iStockPhoto.com/Rob Gentile)
BEYOND THE FRAME RATE: MEASURING HIGH-FREQUENCY FLUCTUATIONS WITH MOTION BLUR
We have developed two techniques for measuring fluctuations, which overcome typical acquisition rate and frequency response limitations of instruments. The key concept is that motion blur can yield information about high-speed dynamics, even above the acquisition rate of an instrument.
SPECTRIN UNFOLDING/REFOLDING KINETICS FROM DYNAMIC FORCE SPECTROSCOPY
We have characterized the force-dependent kinetics of unfolding and refolding for spectrin, an important cytoskeletal protein. This was accomplished by using forward and reverse Dynamic Force Spectroscopy, which employs both ascending and descending ramps of force.
3D HIGH-RESOLUTION, FEEDBACK-STABILIZED OPTICAL TWEEZERS
Our optical tweezers system incorporates high-resolution 3D particle tracking with active feedback for longterm stability, to enable the measurement of both forward and reverse molecular transitions, and near-equilibrium phenomena.