LONG SPACE/TIME SCALE DYNAMICS OF DNA SUPERCOILS: THEORY AND EXPERIMENT

长空间/时间尺度DYNAMICSOF DNA超级线圈：理论和实验这个项目通过扩展机械科学的方法来解决分子生物学中的探索性问题。例如，分子生物学家假设，DNA必须振动，才能将弯曲应变能(或“扭动”)转化为扭转应变能(或“扭转”)，以启动转录和复制的生物过程。这种“扭动到扭曲的转换”发生在DNA超螺旋和跨越纳米到微米的长度尺度上。同样，当DNA片段与某些蛋白质结合时，它是一个动态的过程，作为基因表达的调节机制。我们的目标是通过理论和实验方法来了解DNA在这些过程中的基本动力学性质。我们的理论努力将导致DNA在长时间/空间尺度上的振动理论。我们将DNA链近似为一个长的、非线性的连续体(弹性棒)，它响应于多物理(例如，热、静电、流体、化学结合)力而动态弯曲和扭曲。由此产生的DNA链的非线性动力学理论将被用来探索DNA超级线圈和环是如何演变的，以及这些状态的振动特性。我们的实验努力包括对单分子DNA的雄心勃勃的研究，该研究使用光学陷阱来测量动态响应。这些新颖的理论和实验研究的科学影响包括：1)DNA超线圈在长时间尺度上的振动理论，2)超线圈空间扩展的振动和弛豫时间的实验表征，3)捕捉超螺旋状态之间动态转变的非线性理论，以及4)直接的非线性转变的实验测量。

LONG SPACE/TIME SCALE DYNAMICSOF DNA SUPERCOILS: THEORY AND EXPERIMENTThis project addresses probing questions in molecular biology by extending methods from the mechanical sciences. For instance, molecular biologists have postulated that DNA must vibrate in order to convert bending strain energy (or "writhe") to torsional strain energy (or "twist") to initiate the biological processes of transcription and replication. This "writhe to twist conversion" occurs in DNA supercoils and over lengths scales spanning nanometers to microns. Similarly, the looping of DNA segments when bound to certain proteins is a dynamical process that serves as a regulatory mechanism for gene expression. Our objective is to understand the fundamental dynamical properties of DNA at work in these processes using both theoretical and experimental methods.Our theoretical effort will lead to a vibration theory for DNA over long spatial/time scales. We approximate a strand of DNA as a long and nonlinear continuum (an elastic rod) that dynamically bends and twists in response to multi-physical (e.g., thermal, electrostatic, fluid, chemical binding) forces. The resulting nonlinear dynamical theory for DNA strands will be used to explore how DNA supercoils and loops evolve and the vibration properties of these states. Our experimental efforts include ambitious studies on single-molecule DNA that employ optical traps to measure dynamic response. The scientific impact of these novel theoretical and experimental studies include: 1) a vibration theory for DNA supercoils on long length/time scales, 2) the experimental characterization of the spatially extended vibration and relaxation times of supercoils, 3) a nonlinear theory that captures the dynamic transitions between supercoiled states, and 4) direct experimental measurements of nonlinear transitions.