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

加州大学圣巴巴拉分校的CTS-0103516M.Tirrell在这里提出的工作旨在发展一门科学，即在纳米尺度上自发地将三维空间划分为空间，即受控环境，以实现几个工程目标。目标包括：治疗剂(例如，药物、遗传物质)的受控释放；生物功能成分的受控获取(必要时切换或掩盖活动)；在3D基质中嵌入生物信号(装饰有靶向或“归位”配体的纳米相分离的嵌段共聚多肽)，以及使用表面图案化和模板来制造新颖或定制的结构和环境。四个项目领域包括并组织了我们的总体计划：1.通过脂类包裹创造纳米环境；2.由多肽两亲性创建纳米环境；3.具有层次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造细胞，在某种意义上分离不同功能的区域(没有任何内置自我复制的尝试)。我们的目标是为可能不是自然发生的功能提供仿生结构，并模仿或提供有趣的功能。我们希望包含的功能种类多种多样，从生物的(例如细胞黏附)到非生物的(例如流体连接)。我们将追求的科学是自发地创建具有明确内部和外部的隔室或受限区域的原理。作为一个实际问题，这意味着更深入地研究胶束、囊泡、结构域、小管和其他受控区域的受控形成，作为更大规模纳米组件组装的一部分。我们将合成新的类脂和大分子结构来驱动自组装，这种结构可以包裹某些物种，并可控制地分别在指定区域的内部和外部排除或展示其他物种。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器件相结合的新方法。我们的核心专业知识包括在脂类和大分子结构和相行为方面的丰富经验，这些经验基于合成新分子的强大能力。我们拥有评估和影响生物活性和功能的经验，从细胞黏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。这个团队的成员可以随时获得所有这些工作的表征专业知识和设施：电子显微镜(以多种方式适用于软、湿、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、中子反射仪和有机合成。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。这笔拟议拨款支持的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，这些领域是几个群体的利益高度重叠的领域。通过这种方式，学生们将继续接触到由生物化学家、化学家、物理学家、化学工程师和材料科学家组成的完整的跨学科小组，他们组成了我们的团队。计划作出积极努力，吸引不同群体的学生参加这一项目。我们相信，在这项研究过程中接受培训的学生和同事将在他们的才华上具有非凡的灵活性，因此，由于我们将提供多名顾问、多项技术环境，他们将为在行业或大学的职业生涯做好准备。主计委和共同主计长将管理这一项目，以便在选择要开展的具体项目时不断促进这种跨学科的方法。该项目的努力将为正在开发的名为“生物材料的制备和表征”的新的以实验室为基础的课程注入新的想法、范例和实践经验。

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".