Micro-and nano-mechanical and chemical guidance of neurons

神经元的微纳米机械和化学引导

• 批准号: 7485833
• 负责人: CHRISTINE E SCHMIDT
• 金额: $ 21.29万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485833
• 关键词: Actins; Adhesives; Axon; Cells; Characteristics; Chemicals; Cues; Decision Making; Development; Devices; Embryo; Enzymes; Event; Fluorescence; Fluorescence Microscopy; Goals; Growth; Growth Cones; Growth Factor; Hippocampus (Brain); Image Analysis; Individual; Injury; Knowledge; Lasers; Ligands; Measures; Mechanics; Modeling; Monitor; Nerve; Nerve Growth Factor 1; Nerve Growth Factor Pathway; Nerve Growth Factors; Nerve Regeneration; Neurites; Neurons; Pattern; Probability; Process; Range; Rat-1; Rattus; Research; Research Personnel; Research Project Grants; Scheme; Shapes; Signal Transduction; Standards of Weights and Measures; Stimulus; System; Techniques; Testing; Therapeutic; Work; axon growth; axon guidance; axonal guidance; cell behavior; cell injury; cell type; design; desire; human NTN1 protein; insight; interest; nano; nanofabrication; netrin-1; neuronal cell body; novel; polymerization; programs; repaired; response; therapy design

DESCRIPTION (provided by applicant): The PIs propose to develop novel micro- and nano-fabricated systems that can be used to monitor the simultaneous and competing effects of physical and chemical guidance cues on cell behavior. In particular, this work will focus on understanding how different types of signals "compete" to give rise to axonal extension from neurons. Many groups have studied the impact of different factors individually or in combination, but no one, to our knowledge, has looked at competition between individual factors and combinations of factors. This information will shed insight into the effect of external signals on polarization events and axonal guidance mechanisms involved in development and nerve regeneration, and could potentially provide insight into the desirable characteristics for therapeutic systems to aid nerve repair. To test how different signals contribute to neurite extension, micro- and nano-fabrication techniques will be used to create unique patterned geometries that simultaneously, and yet independently, present the neuron with physical or mechanical cues (e.g., grooves, pillars) and chemical cues (e.g., growth factors, adhesive ligands). In particular, the competition between grooved substrates and immobilized nerve growth factor and netrin-1, and combinations of these stimuli, will be studied for both polarization (axon initiation) and axon elongation and steering responses. Three different device geometries will be fabricated: (1) a "parallel" geometry to test polarization and decisions made at the cell body in response to competition between two stimuli, (2) a "cross-shaped" pattern to test polarization and decisions made at the cell body in response to competition between three or more stimuli, and (3) a "branched" pattern to test axon guidance and decisions made at the growth cone in response to two or more stimuli. Rat embryonic hippocampal neurons will be precisely micropositioned on the devices such that they have equal probability of encountering each separate cue. This will allow the cells to make "decisions" between competing factors by either defining an axon or extending an existing axon toward a desired signal. Image analysis and fluorescence microscopy will be used to measure neurite elongation and monitor the presence of axonal and dendritic markers in response to each cue. The three different proposed devices will be fabricated and optimized as part of Specific Aim 1 and the effects of signal competition on polarization and axon steering in rat hippocampal neurons will be assessed in Specific Aims 2 and 3, respectively.

描述（由申请人提供）：PI建议开发新型微和纳米制造系统，可用于监测物理和化学指导线索对细胞行为的同时和竞争效应。 特别是，这项工作将集中在理解不同类型的信号如何“竞争”引起神经元轴突延伸。 许多研究小组研究了不同因素单独或组合的影响，但据我们所知，没有人研究过单个因素和因素组合之间的竞争。 这些信息将有助于深入了解外部信号对发育和神经再生中涉及的极化事件和轴突引导机制的影响，并可能提供对治疗系统所需特性的深入了解，以帮助神经修复。 为了测试不同的信号如何促进神经突延伸，将使用微米和纳米制造技术来创建独特的图案化几何形状，这些几何形状同时但独立地向神经元呈现物理或机械线索（例如，凹槽，柱）和化学线索（例如，生长因子、粘附配体）。 特别是，沟槽基板和固定的神经生长因子和netrin-1，以及这些刺激的组合之间的竞争，将研究两个极化（轴突起始）和轴突伸长和转向反应。 将制造三种不同的器械几何形状：（1）“平行”几何形状，以测试响应于两个刺激之间的竞争而在细胞体处做出的极化和决定，（2）“十字形”图案，以测试响应于三个或更多个刺激之间的竞争而在细胞体处做出的极化和决定，以及（3）“分支”模式，以测试轴突引导和在生长锥处响应于两个或更多个刺激而做出的决定。 大鼠胚胎海马神经元将被精确地微定位在设备上，使得它们遇到每个单独的线索的概率相等。 这将允许细胞通过定义轴突或将现有轴突延伸到所需信号来在竞争因素之间做出“决定”。 图像分析和荧光显微镜将用于测量神经突伸长和监测轴突和树突标记物的存在，以响应每个线索。 三种不同的拟议设备将作为特定目标1的一部分进行制造和优化，信号竞争对大鼠海马神经元极化和轴突转向的影响将分别在特定目标2和3中进行评估。

项目成果

Computational model provides insight into the distinct responses of neurons to chemical and topographical cues.

• DOI: 10.1007/s10439-008-9613-x
• 发表时间: 2009-02
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Forciniti, Leandro;Schmidt, Christine E.;Zaman, Muhammad H.
• 通讯作者: Zaman, Muhammad H.

A chemically polymerized electrically conducting composite of polypyrrole nanoparticles and polyurethane for tissue engineering.

• DOI: 10.1002/jbm.a.33128
• 发表时间: 2011-09-15
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
• 影响因子: 4.9
• 作者: Broda, Christopher R.;Lee, Jae Y.;Sirivisoot, Sirinrath;Schmidt, Christine E.;Harrison, Benjamin S.
• 通讯作者: Harrison, Benjamin S.

Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering.

• DOI: 10.1007/s10544-011-9568-9
• 发表时间: 2011-12
• 期刊: Biomedical microdevices
• 影响因子: 2.8
• 作者: Suri S;Han LH;Zhang W;Singh A;Chen S;Schmidt CE
• 通讯作者: Schmidt CE