Research strands:
Study of forces in single molecules and cells
The development of ultrasensitive force transducers has made it possible to directly measure inter- and intramolecular forces between and within individual macromolecules. Single molecule force measurements have been made in biomolecular systems with the atomic force microscope (AFM), micropipette, optical tweezers, flow chamber, and magnetic tweezers, with each technique having an optimal force and displacement sensitivity range. The micropipette and AFM have been used to study the physical behavior of intermolecular interactions and individual molecules under tensile load. Torque has been applied with magnetic tweezers, which has been used to characterize the influence of writhe on the interaction of proteins with DNA and the mechanical properties of F-actin networks in living cells. These measurements have provided a basis for understanding the behavior of biomolecular systems under non-equilibrium conditions and the intramolecular forces responsible for macromolecule structure. This has resulted in new insight into the important role force plays in cellular behavior.
This research group has played an active role in the study of forces in biomolecular systems. Our early work focused on using the AFM to understand the nature of specific molecular interactions under load. This included pioneering measurements of the influence of force on the bond lifetime of streptavidin-biotin and complementary strands of DNA. This work included initial work on the calibration of the AFM to allow quantitative force measurements to be made and the developed novel surface chemistries to immobilize macromolecules on the AFM probe and surface. More recently, the AFM has been applied to the study of the mechanical properties of cells, which we believe will provide new insight into the molecular mechanisms of cell motility and signaling.
As single molecule force measurements have been applied to more biomolecular systems, higher measurement sensitivity has become increasingly desirable. The magnetic tweezers technique can, in principle, be used to transduce piconewton (pN) forces to superparamagnetic microparticles. This laboratory has developed new magnetic transducers (described below) that make it possible to simultaneously measure the behavior of hundreds of ligand-receptor pairs. This technique has been used to characterize the force-bond lifetime behavior of the mouse IgG type 2a-protein A interaction and screen phage displayed libraries.
The development of ultrasensitive force transducers has made it possible to directly measure inter- and intramolecular forces between and within individual macromolecules. Single molecule force measurements have been made in biomolecular systems with the atomic force microscope (AFM), micropipette, optical tweezers, flow chamber, and magnetic tweezers, with each technique having an optimal force and displacement sensitivity range. The micropipette and AFM have been used to study the physical behavior of intermolecular interactions and individual molecules under tensile load. Torque has been applied with magnetic tweezers, which has been used to characterize the influence of writhe on the interaction of proteins with DNA and the mechanical properties of F-actin networks in living cells. These measurements have provided a basis for understanding the behavior of biomolecular systems under non-equilibrium conditions and the intramolecular forces responsible for macromolecule structure. This has resulted in new insight into the important role force plays in cellular behavior.
This research group has played an active role in the study of forces in biomolecular systems. Our early work focused on using the AFM to understand the nature of specific molecular interactions under load. This included pioneering measurements of the influence of force on the bond lifetime of streptavidin-biotin and complementary strands of DNA. This work included initial work on the calibration of the AFM to allow quantitative force measurements to be made and the developed novel surface chemistries to immobilize macromolecules on the AFM probe and surface. More recently, the AFM has been applied to the study of the mechanical properties of cells, which we believe will provide new insight into the molecular mechanisms of cell motility and signaling.
As single molecule force measurements have been applied to more biomolecular systems, higher measurement sensitivity has become increasingly desirable. The magnetic tweezers technique can, in principle, be used to transduce piconewton (pN) forces to superparamagnetic microparticles. This laboratory has developed new magnetic transducers (described below) that make it possible to simultaneously measure the behavior of hundreds of ligand-receptor pairs. This technique has been used to characterize the force-bond lifetime behavior of the mouse IgG type 2a-protein A interaction and screen phage displayed libraries.
