A Nanomechanical Toolkit to Guide Membrane Structure and Dynamics

项目总结 细胞膜分隔和调节生化反应，并促进生物分子的运输 形成了多样的、动态的结构。用于各种应用，从基础生物学研究到 膜传输到生物医学应用，例如药物输送，希望控制膜 使用体外方法精确地进行结构和动力学研究。这在过去一直很困难，因为缺乏 多功能、高精度工具，用于制造和操纵薄膜。受蛋白质机器的启发 这种支架和雕刻膜，我们建议建立形状明确的DNA纳米结构和 运动作为膜工程的纳米级机械工具。这个想法是为了引导形成和 膜相互作用的动态DNA纳米结构对脂双层的变形 分子，从而将DNA结构的可编程特征传递到支架膜上。 这项建议建立在我们最近演示的DNA纳米技术支持的膜工程基础上 方法，并专注于通过设计DNA结构来构建精确和通用的工具库 复杂的自组装和重新配置机制。我们还将包括膜重塑 蛋白质复合体进入DNA纳米支架，并调节蛋白质的集体行为。最新的 开发的工具包将测试其生成各种几何形状的所需膜曲率的能力 以及以空间和时间控制的方式的维度。我们预计该项目将(1)建立一个 适用于膜生物物理定量研究的平台，(2)交付用于分类的原型设备 蛋白质通过它们的膜曲率识别能力，以及(3)在 DNA纳米技术和细胞生物学。

PROJECT SUMMARY Cell membranes compartmentalize and modulate biochemical reactions and facilitate biomolecule transport by forming diverse and dynamic structures. For a variety of applications ranging from basic biological study of membrane trafficking to biomedical applications such as drug delivery, it is desirable to control membrane structure and dynamics precisely using in vitro methods. This has been difficult in the past due to the lack of versatile, high-precision tools to manufacture and manipulate membranes. Inspired by the protein machineries that scaffold and sculpt membranes, we propose to build DNA nanostructures with well-defined shape and motion as nanoscale mechanical tools for membrane engineering. The idea is to guide the formation and deformation of lipid bilayers using dynamic DNA nanostructures equipped with membrane-interacting molecules, hence transducing the programmable features of the DNA structures to the scaffolded membranes. This proposal builds on our recently demonstrated DNA-nanotechnology enabled membrane engineering methods, and focuses on building an arsenal of precise and versatile tools by designing DNA structures with sophisticated self-assembly and reconfiguration mechanisms. We will also incorporate membrane-remodeling protein complexes into DNA nanoscaffolds and modulate the proteins' collective behaviors. The newly developed toolkit will be tested for their ability to generate desired membrane curvatures of various geometry and dimensions in spatially and temporally controlled manner. We expect the project to (1) establish an adaptable platform for the quantitative study of membrane biophysics, (2) deliver prototype devices for sorting proteins by their membrane-curvature recognition capability, and (3) engender a unique interface between DNA nanotechnology and cell biology.