Thrust 3: Molecular Propulsion: Chemical Sensing and Chemotaxis of DNA Driven by RNA Polymerase

1. University of Wisconsin-Madison NSEC: Templated Synthesis and Assembly at the Nanoscale Thrust 3: Molecular Propulsion: Chemical Sensing and Chemotaxis of DNA Driven by RNA Polymerase Yu, H., K. Jo, K.L. Kounovsky, J.J. de Pablo, and D.C. Schwartz For the first time, DNA molecules have been fashioned into tiny “smart molecules” that move in water toward the very fuel powering their on-board motors. These motors are enzymes (RNA polymerase) that bind to DNA molecules and act as tiny motors that move water, while they actively transcribe DNA into complementary RNA molecules (Fig. 1). This activity closely mimics what some bacteria do while seeking nutrition and provides DNA molecules with sensing capabilities for guiding their motion through water, but we have now miniaturized and enormously simplified this complex activity to the level of a single DNA molecule. Because a given DNA molecule independently reacts to its environment, smart molecules will become the basis for designing new types of experimental systems where the very components themselves make individualized decisions affecting experimental outcome. DNA molecules, long known as repositories for genetic information, have been exploited for facile construction of objects by utilizing their programmable structural advantages mediated by sequence composition. Our Thrust 3 research advances this later concept by the discovery that DNA molecules, under simple transcriptional action, display autonomous motion that is not masked by random Brownian diffusion in free solution. Strikingly, such motion is also guided by gradients of reaction substrates in ways mimicking bacterial chemotaxis. Essentially, we have made a system that enables DNA molecules to actually “swim” and can be made to swim toward factors powering their motion. We have named this newly discovered action—“molecular propulsion.” Perhaps, the most surprising aspect of this discovery is that although RNA polymerase action has been extensively studied over the last few decades by means that tether either DNA templates or the polymerase, but never shown to exhibit enhanced transport properties in free solution. Our demonstration of transcriptionally mediated chemotaxis establishes a precedent for the autonomous control of individual DNA molecules based on their local chemical environment, and template, or polymerase composition (Fig.2). This new phenomenon will likely become the basis for new types of massively parallel assays where the components themselves configure experimental design. Fig. 2 Summary of actions associated with molecular propulsion Fig. 1. Molecular propulsion is powered by RNA polymerase interacting with a DNA molecule. NSF Award Number 0832760 PI: Paul Nealey University of Wisconsin – Madison