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A Nanomechanical Toolkit to Guide Membrane Structure and Dynamics

指导膜结构和动力学的纳米机械工具包

基本信息

批准号：
10378021
负责人：
Chenxiang Lin
金额：
$ 33.5万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2023-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10378021
关键词：
ATG3 gene Address Artificial Membranes Behavior Binding Biochemical Biochemical Reaction Biochemistry Biological Biophysics Bioreactors Biotechnology Calcium Cell membrane Cell physiology Cells Cellular biology Chemistry Complement Complex Cues Custom Cytokinesis DNA DNA Structure Development Devices Dimensions Drug Delivery Systems Engineering Enzymes Eukaryotic Cell Event Foundations Future Generations Geometry Goals In Vitro Kinetics Knowledge Lipid Bilayers Lipids Liposomes Maintenance Mechanics Mediating Membrane Membrane Fusion Methods Modeling Modification Molecular Motion Nanostructures Nanotechnology Organelles Pathologic Philology Phosphorylation Physiological Process Property Protein Sortings Proteins Resolution Rest SNAP receptor Shapes Stimulus Structure Surface System Techniques Tertiary Protein Structure Testing Uncertainty Vesicle Virus Diseases Work base cellular pathology design experimental study improved in vivo insight nanocage nanomechanics nanoscale outcome prediction preference programs protein complex prototype scaffold self assembly stoichiometry success synthetic biology tool trafficking

项目摘要

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.

项目摘要细胞膜分隔和调节生化反应，并促进生物分子的运输，形成多样的动态结构。用于各种应用，从基础生物学研究，膜运输到生物医学应用如药物递送，期望控制膜运输。结构和动力学精确使用体外方法。这在过去一直很困难，因为缺乏用于制造和操作膜的多功能、高精度工具。受蛋白质机器的启发我们建议构建具有明确形状的DNA纳米结构，作为膜工程的纳米机械工具。这个想法是为了指导形成和使用配备有膜相互作用的动态DNA纳米结构的脂质双层的变形分子，因此将DNA结构的可编程特征转导到支架膜。这项建议建立在我们最近展示的DNA纳米技术使膜工程方法，并专注于通过设计DNA结构，复杂的自我组装和重新配置机制。我们还将结合膜重塑蛋白质复合物进入DNA纳米支架并调节蛋白质的集体行为。新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空间和时间受控方式的尺寸。我们希望该项目（1）建立一个适用于膜生物物理学定量研究的平台，（2）提供用于分选的原型装置蛋白质的膜曲率识别能力，和（3）产生一个独特的界面之间 DNA纳米技术和细胞生物学。