DNA Free Energy Landscapes and RNA Nano-Self-Assembly Using Atomic Force Microscopy

[摘要] There is an important conceptual lesson which has long been appreciated by thosewho work in biophysics and related interdisciplinary fields. While the extraordinarybehavior of biological matter is governed by its detailed atomic structure and randomfluctuations, and is therefore difficult to predict, it can nevertheless be understoodwithin simplified frameworks. Such frameworks model the system as consisting of onlyone or a few components, and model the behavior of the system as the occupationof a single state out of a small number of states available. The emerging widespreadapplication of nanotechnology, such as atomic force microscopy (AFM), has expandedthis understanding in eye-opening new levels of detail by enabling nano-scale control,measurement, and visualization of biological molecules. This thesis describes twoindependent projects, both of which illuminate this understanding using AFM, butwhich do so from very different perspectives.The organization of this thesis is as follows. Chapter 1 begins with an experimentalbackground and introduction to AFM, and then describes our setup in bothsingle-molecule manipulation and imaging modes. In Chapter 2, we describe thefirst project, the motivation for which is to extend methods for the experimentaldetermination of the free energy landscape of a molecule. This chapter relies onthe analysis of single-molecule manipulation data. Chapter 3 describes the secondproject, the motivation for which is to create RNA-based nano-structures suitable forfuture applications in living mammalian cells. This chapter relies mainly on imaging.Chapters 2 and 3 can thus be read and understood separately.

[发布机构] Rice University

[效力级别] energy