Bioengineering Single Crystal Growth

ID: MPS/DMR/BMAT(7623) 0805313 PI: Joester， Derk ORG: Northwestern university标题：生物工程单晶生长知识优势：尽管生物矿化组织具有非常吸引人的特性，生物启发材料合成取得了巨大进展，但许多生物晶体生长的标志尚未在体外复制：多晶控制，弯曲和/或分支单晶，和纳米尺度控制的有机-无机复合材料。通过开发一种替代散装材料合成的生物技术，可以获得很多成果。在这个提议中，PI将探索海胆胚胎原代间质细胞（PMCs）的微模式细胞培养作为指导单晶合成的细胞机制的手段。以这种方式，该项目将利用一个完全有能力的合成引擎，并试图重新编程。这将为研究并最终在体外进行逆向工程提供基础。以下具体任务将通过引导生物沉积来探索和发展工程单晶形状，连通性和更大的复合结构的范围和限制：(1)开发微图案来控制pmc在表面上的放置。从而指导生物沉积单个方解石（CaCO3）晶体。特别是，建立由血管内皮生长因子（VEGF）诱导的模式地形、粘附性、趋化性，以及限制细胞数量和密度。(2)探索连接模式，以重现两个单独的单晶元素的生物三辐射分支或融合。结合简单的形状和连接日益复杂的晶体形状和连接在2D和3D。(3)通过包括活细胞成像、红外和拉曼显微镜以及电子显微镜成像在内的互补技术，进一步表征生物晶体生长机制，包括矿物/蛋白质运输路线、无定形前体相和无定形到晶体的转变。更广泛的影响：拟议的研究有望在利用生物合成矿化途径来制造有用的陶瓷结构方面取得重大进展。该项目还包括一项全面的研究和教育整合计划。该项目将开设四分之一的生物矿化本科课程，旨在培养学生的沟通技巧，让他们接触专业的同行评审，并评估他们的分析能力。学生们将通过一个在线的、公共的、由学生编写、审查和编辑的WIKI来传播他们所获得的知识。将举办一项设计比赛，开发新的细胞培养装置，以引导晶体生长，从而吸引学生参与PI？并在一个跨学科的项目中运用他们的工程技能。PI的本科生研究机会？美国实验室将在生物相关领域提供高度跨学科的交叉培训，如海胆养殖、细胞培养和活细胞成像，这些活动将补充洁净室光刻和先进成像技术的材料表征培训。面向高中学生的推广活动将以芝加哥、罗杰斯公园和埃文斯顿等多种族社区为目标。由于目前实验室的所有研究生都是女性，因此将特别关注积极的女性榜样的投射。将与高中科学教师、工程和生物材料课程模块、西北校区参观和夏季实习项目一起组织。

ID: MPS/DMR/BMAT(7623) 0805313 PI: Joester, Derk ORG: Northwestern UniversityTitle: Bioengineering Single Crystal GrowthINTELLECTUAL MERIT: Despite the highly attractive properties of biological mineralized tissues and great recent progress in bio-inspired materials synthesis, many of the hallmarks of biological crystal growth have yet to be reproduced in vitro: polymorph control, curving and/or branching single crystals, and nm scale control of organic-inorganic composites. Much could be gained by developing a biotechnological alternative to bulk materials synthesis. In this proposal the PI will explore micro-patterned cell culture of sea urchin embryonic primary mesenchyme cells (PMCs) as a means to guide the cellular machinery responsible for single crystal synthesis. In this way the project will take advantage of a fully capable synthetic engine and attempt to reprogram it. This will then provide the basis for investigating and ultimately reverse engineering it in vitro. The following specific tasks will be pursued to explore and develop the range and limits of engineering single crystal shape, connectivity, and larger composite structures by guided biological deposition: (1) Develop micro-patterning to control the placement of PMCs on a surface. In this way, guide the biological deposition of single calcite (CaCO3) crystals. In particular, establish pattern topography, adhesiveness, chemotaxis induced by vascular endothelial growth factor (VEGF), and limiting cell numbers and densities. (2) Explore junction patterns to reproduce the biological tri-radiate branching or fusion of two individual single crystalline elements. Combine simple shapes and junctions for increasingly complex crystal shape and connectivity in 2D and 3D. (3) Further characterize the biological crystal growth machinery with respect to routes of mineral/protein trafficking, amorphous precursor phases, and amorphous-to crystalline transitions by a complementary suite of techniques including live cell imaging, IR and Raman microscopy, and electron microscopic imaging. BROADER IMPACTS: The proposed research promises a major advance in harnessing biosynthetic mineralization pathways to create useful ceramic structures. The project also includes a thorough plan for integration of research and education. The PI will develop a full quarter undergraduate course in biomineralization designed to train students in communications skills, expose them to professional peer review, and assess their analytical skills. Students will disseminate the knowledge gained through an online, public access WIKI that will be written, reviewed, and edited by students. A design competition will be held to develop new cell culture devices for guided crystal growth and thus draw students into questions actively researched in the PI?s laboratory and engage their engineering skills in a trans-disciplinary project. Undergraduate research opportunities in the PI?s lab will provide highly interdisciplinary cross training in bio-related areas such as sea urchin husbandry, cell culture, and live cell imaging, and these activities will complement training in clean room photolithography and materials characterization by advanced imaging techniques. Outreach to high school students will be targeted to ethnically diverse neighborhoods of Chicago, Rogers Park, and Evanston. As all current graduate students in the lab are female, an especially focused projection of positive female role models will be achieved. In conjunction with high school science teachers, engineering and biomaterials class modules, visits on the Northwestern Campus, and a summer internship program will be organized.