Nanomechanics of Macromolecules and Macromolecular Assemblies: From DNA Packaging to Force-Actuated Membrane Proteins

单分子生物物理测量的出现和结构生物学的进步使构建一系列生物现象的机械模型成为可能。这项工作的目的是研究两大类问题：i)DNA在病毒和真核细胞中堆积的机制；ii)机械激活离子通道的物理学。这项工作的目的是将这些系统的连续介质和原子模型与旨在探索其特定机械作用的实验联系起来。特别是，我们将研究DNA在病毒中的包装和病毒感染过程中DNA的排出过程。此外，我们将研究DNA序列决定其弹性性质的方式，以及这反过来如何影响真核染色体的自组装过程。我们在机械激活的膜通道上的努力将集中在检查脂双层膜的张力和离子通道的构象变化之间的耦合。

The advent of single molecule biophysical measurements in conjunction with advances instructural biology makes it possible to construct mechanical models of a range of biological phenomena. The aim of the work proposed here is to investigate two broad classes of problems:i) the mechanics of DNA packing both in viruses and eucaryotic cells and ii) the physics of mechanically activated ion channels. The objective of this work is to link continuum and atomistic models of these systems with experiments aimed at probing their specific mechanical action. In particular, we will examine both the packing of DNA in viruses and the process of ejection of that DNA during the viral infection process. In addition, we will study the way in which the DNA sequence dictates its elastic properties and how this in turn affects the self-assembly process of the eucaryotic chromosome. Our efforts on mechanically activated membrane channels will be centered on examining the coupling between tension in the lipid bilayer membrane and conformational changes in the ion channel.