NIRT: Creating Functional Nano-Environments by Controlled Self-Assembly

NIRT：通过受控自组装创建功能性纳米环境

• 批准号: 0103516
• 负责人: Matthew Tirrell
• 金额: $ 142.5万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0103516&HistoricalAwards=false
• 关键词: NIRT; Creating; Functional; Nano; Environments

AbstractCTS-0103516M.Tirrell, University of California-Santa BarbaraThe work proposed here aims to develop the science of spontaneously dividing three-dimensional space into compartments, that is, into controlled environments, at the nanometer size scale, in order to accomplish several engineering objectives. The objectives include: controlled release of therapeutic agents (e.g., drugs, genetic materials); controlled access to biofunctional components (switching or masking activities when desirable); embedding biological signaling within 3D matrices (nano-phase-separated block co-polypeptides decorated with targeting or "homing" ligands) and using surface patterning and templating to produce novel or tailored structures and environments. Four project areas encompass and organize our overall plan: 1. Creating nano-environments via lipid encapsulation; 2. Nano-environments from peptide amphiphiles; 3. Amphiphilic block copolypeptides with hierarchical structures; 4. Patterned surfaces for self-assembly. The work we will do is conceptually similar to creating artificial cells in the sense of separating regions for different functions (without any attempt to build in self-replication). We are aiming toward bio-mimetic structures for functions that may not be naturally occurring, and that mimic or supply interesting functionality. The kinds of functions we wish to incorporate vary from biological (e.g., cell adhesion) to non-biological (e.g., fluid connectivity).The science we will pursue is the principle of spontaneously creating compartments or confined regions with a definite inside and outside. As a practical matter, this means delving deeper into controlled formation of micelles, vesicles, domains, tubules and other controlled regions, as part of larger assemblies of nanoscale components. We will synthesize new lipid-like and macromolecular architectures to drive self-assembly in ways that can encapsulate some species and exclude or display others, controllably, on the interiors and exteriors, respectively, of defined regions. Our research will produce new materials for biomedical applications, new therapeutic approaches based on controllable binding and transport processes and new ways of integrating biological structures with semiconductor fabricated devices. Our core expertise includes extensive experience with lipid and macromolecular structure and phase behavior, based on substantial ability to synthesize new molecules. We have experience with assessing and influencing biological activities and functions, ranging from cell adhesion, to drug delivery and gene transfection, to the roles of metal ions in growth processes and pathological conditions. Characterization expertise and facilities for all of this work are readily available among the members of this collaboration: electron microscopy (adapted in several ways for soft, wet, biological samples), scanning probe nicroscopies, optical microscopy (with fluorescence, confocal, interference and video capabilities), surface force measurements, x-ray and neutron scattering, neutron reflectometry and organic synthesis.The interdisciplinary talents of this team are essential to educate students broadly in the new fields of nanotechnology and biotechnology. The five graduate students and one postdoctoral fellow supported by this proposed grant will work in broad areas of the overall project where interests of several groups overlap strongly. In this way, the students will have continued exposure to the full interdisciplinary group of biochemists, chemists, physicists, chemical engineers and materials scientists that make up our team. An active effort is planned to attract a diverse population of students to this project. We believe that the students and fellow trained in the course of this research will be extraordinarily flexible in their talents, and therefore exceptionally, well-prepared for careers in industry or universities, because of the multiple advisor, multiple technique environment we will provide. The PI and co-PI's will manage this project to continuously promote this interdisciplinary approach in the selection of specific projects to be pursued. The efforts from this project will feed new ideas, examples and practical experience into a new laboratory-based course under development entitled, "Biomaterials Preparation and Characterization".

本文提出的工作旨在发展在纳米尺度上自发地将三维空间划分成隔间，即划分成受控环境的科学，以实现几个工程目标。目标包括：治疗剂（例如，药物、遗传物质）;控制生物功能组分的进入（需要时转换或掩蔽活性）;将生物信号嵌入3D基质（用靶向或“归巢”配体修饰的纳米相分离的嵌段共多肽）中，并使用表面图案化和模板化来产生新的或定制的结构和环境。四个项目领域涵盖并组织我们的总体计划：1.通过脂质包封形成纳米环境; 2.来自肽两亲物的纳米环境; 3.具有分级结构的两亲性嵌段共聚肽; 4.用于自组装的图案化表面。我们将做的工作在概念上类似于创造人工细胞，即为不同的功能分离区域（没有任何自我复制的尝试）。我们的目标是生物模拟结构的功能，可能不是自然发生的，模仿或提供有趣的功能。我们希望结合的功能种类从生物学的（例如，细胞粘附）到非生物（例如，流体连通性）。我们将追求的科学是自发地创造具有明确内部和外部的隔间或封闭区域的原理。实际上，这意味着更深入地研究胶束、囊泡、域、小管和其他受控区域的受控形成，作为纳米级组件的更大组件的一部分。我们将合成新的类脂质和大分子结构，以驱动自组装的方式，可以封装一些物种，并排除或显示其他，可控地，分别在内部和外部的定义区域。我们的研究将产生用于生物医学应用的新材料，基于可控结合和传输过程的新治疗方法，以及将生物结构与半导体制造设备集成的新方法。我们的核心专业知识包括在脂质和大分子结构和相行为方面的丰富经验，以及合成新分子的能力。我们拥有评估和影响生物活性和功能的经验，从细胞粘附到药物输送和基因转染，再到金属离子在生长过程和病理条件中的作用。所有这些工作的表征专业知识和设施都可以在该合作的成员中随时获得：电子显微镜（以多种方式适用于柔软、潮湿的生物样品）、扫描探针显微镜、光学显微镜（具有荧光、共焦、干涉和视频功能），表面力测量，X射线和中子散射，该团队的跨学科人才对于在纳米技术和生物技术的新领域广泛教育学生至关重要。五名研究生和一名博士后研究员将在整个项目的广泛领域工作，其中几个团体的利益强烈重叠。通过这种方式，学生将继续接触组成我们团队的生物化学家，化学家，物理学家，化学工程师和材料科学家的完整跨学科小组。计划积极努力吸引各种学生参加这一项目。我们相信，在这项研究的过程中培养的学生和研究员将在他们的人才非常灵活，因此，特别是，在行业或大学的职业生涯做好了充分的准备，因为我们将提供多个顾问，多技术环境。主要研究者和共同主要研究者将管理该项目，以在选择具体项目时不断推广这种跨学科方法。该项目的努力将为正在开发的题为“生物材料制备和表征”的新的实验室课程提供新的想法、实例和实践经验。