Designing active DNA-based constructs as protein-inspired transmembrane structures

磷脂膜包裹着每一个细胞，是所有生物的重要信号平台。跨膜蛋白嵌入其中，是负责膜特性的分子机器。它们相对复杂的结构允许对双层形状和脂质成分进行高水平的控制。这种程度的控制使蛋白质启发的跨膜结构成为一种理想的工具，而这些结构的开发也成为一个充满活力的研究领域。DNA是目前探索的一种潜在的模拟蛋白质的构建单元，因为它可以很容易地通过互补碱基配对进行修饰、设计和组装。从合成的DNA-折纸膜通道开始，开发了一系列的结构，所有这些结构都是为了通过疏水锚定插入到膜中。本项目旨在为这些基于DNA的跨膜结构的智能设计奠定基础。主要研究了以下几个方面的问题：1.由于跨膜DNA的强电荷性，它可以重新排列毛孔内的脂类。该项目旨在创造一种以蛋白质为灵感的结构，展示对这种脂质排列的控制。在生物环境中，离子浓度是非常微调的。然而，目前的DNA结构需要大量的阳离子才能正确折叠。该项目将探索DNA-脂质相互作用对阳离子的依赖性。目前DNA结构的插入效率相对较低。该项目旨在评估表面活性剂对插入的影响，以及探索促进DNA-脂质相互作用的基本设计原则。这个项目是基于一项实验研究。上述结构将被设计和折叠，然后在模型细胞膜上进行测试。光学技术以及单分子测量将是这项工作的基础。

Phospholipid membrane envelopes every cell, and is an important signaling platform for all organisms. Embedded within it, transmembrane proteins are molecular machines responsible for membrane's properties. Their relatively complex structure allows for a high level of control over bilayer shape and lipid composition. Such degree of control makes protein-inspired transmembrane structures a desirable tool, and the development of these a vibrant field of study.One of the materials currently explored as a prospective protein-mimicking building block is DNA, due to the ease with which it may be modified, designed and assembled using complementary base pairing. Starting with a synthetic DNA-origami membrane channel, a whole variety of structures was developed, all designed to insert into the membrane via hydrophobic anchors. This project aims to lay foundation under the smart design of these DNA-based transmembrane structures. It focuses particularly on the problems listed below:1. Due to its strong charge, membrane-spanning DNA rearranges lipids within the pore. The project aims to create a protein-inspired structure exhibiting control over this lipid arrangement.2. In biological environment ionic concentration is very finely tuned. However, the current DNA structures require high amounts of cations in order to fold properly. The project will explore the dependency of DNA-lipid interactions on cations.3. The insertion efficiency of current DNA structures is relatively low. The project aims to assess the effects of surfactants on the insertion, as well as explore basic design principles that will facilitate DNA-lipid interactions. This project is based on an experimental research. The aforementioned structures will be designed and folded, then tested on model cell membranes. Optical techniques as well as single-molecule measurements will be the foundation of the work.