Leveraging 2D and 3D interactions to understand structural transitions in model and cell membranes from molecular to micron scales

所有的细胞都被细胞膜包围着，这个项目将直接测量细胞膜模型内分子的分布。这项研究的结果将是重要的，对社会有益，因为分布可以决定膜中蛋白质的功能和细胞的生死。额外的社会效益是，该项目将产生新的微流体装置设计和新的方案，通过低温电子显微镜在纳米尺度上观察膜。这些设计和方案将在科学出版物中广泛提供。该项目还将为学生研究人员在科学和工程领域具有挑战性的职业生涯做好准备。研究生和本科生的研究人员将产生样本，检验假设，分析他们的数据，在会议上展示他们的结果，并发表他们的结果。该项目还包括其他活动，旨在通过外展项目激励、培训和指导下一代科学家和公民。许多类型的生物物理膜自发分解成富含特定脂质（和蛋白质）类型的微米级液体结构域。系统的复杂性从仅由几种脂质类型组成的“简单”模型膜到源自细胞的复杂膜或酵母中的细胞器膜不等。该研究将回答以下生物学动机问题：膜物理参数的变化如何影响膜中液体域的大小、形状和转变温度？膜与体溶液的相互作用如何影响膜的形状和混相转变？膜脱混如何影响肽的结构和分配？除了回答这些问题之外，该项目的目标是通过展示物理现象如何为理解复杂的生物膜系统提供新方法，将由此产生的发现转化为生物界。将采用的工具包括荧光显微镜、微流体和冷冻电子显微镜。该项目将成为培养研究生和本科生在科学和工程领域具有挑战性的职业的工具。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

All cells are surrounded by a cell membrane, and this project will directly measure the distributions of molecules within models of cell membranes. The results of this research will be important and of benefit to society because the distribution can determine how a protein in the membrane functions and whether a cell lives or dies. Additional societal benefit is that the project will generate new designs for microfluidic devices and new protocols for visualizing membranes on nanometer scales by cryo-electron microscopy. The designs and protocols will be made widely available in scientific publications. This project will also prepare student researchers for challenging careers in science and engineering. Graduate and undergraduate researchers will produce samples, test hypotheses, analyze their data, present their results at conferences, and publish their results. The project includes additional activities designed to inspire, train, and mentor the next generation of scientists and citizens through outreach projects. Many types of biophysical membranes spontaneously demix into micron-scale liquid domains enriched in specific lipid (and protein) types. The systems range in complexity from "simple" model membranes composed of only a few lipid types, to complex membranes derived from cells, or organelle membranes in yeast. The research will answer the following biologically-motivated questions: How do changes in membrane physical parameters affect the size, shape, and transition temperatures of liquid domains in membranes? How do interactions of membranes with bulk solutions affect membrane shapes and miscibility transitions? How does membrane demixing affect peptide structure and partitioning? Beyond answering these questions, the goals of the project are to translate the resulting discoveries to the biology community by showing how physical phenomena suggest new approaches for understanding complex biomembrane systems. The tools that will be employed include fluorescence microscopy, microfluidics, and cryo-electron microscopy. The project will be a vehicle for training graduate and undergraduate students for challenging careers in science and engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.