Papers by Dr. Anita Goel, MD, PhD
Nature Nanotechnology, 2008
Living systems use biological nanomotors to build life's essential molecules-such as DNA and prot... more Living systems use biological nanomotors to build life's essential molecules-such as DNA and proteins-as well as to transport cargo inside cells with both spatial and temporal precision. Each motor is highly specialized and carries out a distinct function within the cell. Some have even evolved sophisticated mechanisms to ensure quality control during nanomanufacturing processes, whether to correct errors in biosynthesis or to detect and permit the repair of damaged transport highways. In general, these nanomotors consume chemical energy in order to undergo a series of shape changes that let them interact sequentially with other molecules. Here we review some of the many tasks that biomotors perform and analyse their underlying design principles from an engineering perspective. We also discuss experiments and strategies to integrate biomotors into synthetic environments for applications such as sensing, transport and assembly.
Nanotechnology, 2008
Living systems use biological nanomotors to build life's essential molecules-such as DNA and prot... more Living systems use biological nanomotors to build life's essential molecules-such as DNA and proteins-as well as to transport cargo inside cells with both spatial and temporal precision. Each motor is highly specialized and carries out a distinct function within the cell. Some have even evolved sophisticated mechanisms to ensure quality control during nanomanufacturing processes, whether to correct errors in biosynthesis or to detect and permit the repair of damaged transport highways. In general, these nanomotors consume chemical energy in order to undergo a series of shape changes that let them interact sequentially with other molecules. Here we review some of the many tasks that biomotors perform and analyse their underlying design principles from an engineering perspective. We also discuss experiments and strategies to integrate biomotors into synthetic environments for applications such as sensing, transport and assembly.
Proceedings of the National Academy of Sciences, 2001
Recent experiments have measured the rate of replication of DNA catalyzed by a single enzyme movi... more Recent experiments have measured the rate of replication of DNA catalyzed by a single enzyme moving along a stretched template strand. The dependence on tension was interpreted as evidence that T7 and related DNA polymerases convert two (n ؍ 2) or more single-stranded template bases to double helix geometry in the polymerization site during each catalytic cycle. However, we find structural data on the T7 enzyme-template complex indicate n ؍ 1. We also present a model for the ''tuning'' of replication rate by mechanical tension. This model considers only local interactions in the neighborhood of the enzyme, unlike previous models that use stretching curves for the entire polymer chain. Our results, with n ؍ 1, reconcile force-dependent replication rate studies with structural data on DNA polymerase complexes.
Recent single-molecule experiments reveal that mechanical tension on DNA can control both the spe... more Recent single-molecule experiments reveal that mechanical tension on DNA can control both the speed and direction of the DNA polymerase motor. We present a theoretical description of this tension-induced ''tuning'' and ''switching.'' The internal conformational states of the enzyme motor are represented as nodes, and the allowed transitions between states as links, of a biochemical network. The motor moves along the DNA by cycling through a given sequence of internal states. Tension and other external control parameters, particularly the ambient concentrations of enzyme, nucleotides, and pyrophosphates, couple into the internal conformational dynamics of the motor, thereby regulating the steady-state flux through the network. The network links are specified by bulk-phase kinetic data (in the absence of tension), and rudimentary models are used to describe the dependence on tension of key links. We find that this network analysis simulates well the chief results from single-molecule experiments including the tension-induced attenuation of polymerase activity, the onset of exonucleolysis at high tension, and insensitivity to large changes in concentration of the enzyme. A major dependence of the switching tension on the nucleotide concentration is also predicted.
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Papers by Dr. Anita Goel, MD, PhD