Modulating 3D Cellular Connectivity Via Spatially-Controlled Programmable Bonding

通过空间控制的可编程绑定调节 3D 蜂窝连接

• 批准号: 10195452
• 负责人: Brian R Meckes
• 金额: $ 21.04万
• 依托单位: UNIVERSITY OF NORTH TEXAS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10195452
• 关键词: 3-Dimensional; 3D Print; Address; Animal Model; Area; Base Pairing; Behavior; Biocompatible Coated Materials; Biological; Biological Process; Biomedical Research; Cell Communication; Cell Therapy; Cells; Chemical Engineering; Chemicals; Chemistry; Cicatrix; Coculture Techniques; Communication; Complex; Cues; DNA; DNA Sequence; Degenerative Disorder; Degenerative polyarthritis; Development; Developmental Process; Disease; Engineering; Environment; Future; Gene Expression; Germ Cells; Goals; Immunology; In Vitro; Individual; Intercellular Junctions; Lead; Libraries; Location; Mediating; Methods; Modeling; Nanotechnology; Natural regeneration; Neoplasm Metastasis; Oligonucleotides; Pattern; Play; Population; Printing; Process; Research; Research Proposals; Resolution; Role; Signal Transduction; Site; Surface; System; Techniques; Technology; Testing; Therapeutic; Tissue Engineering; Tissues; Vision; angiogenesis; base; cell assembly; cell behavior; cell type; design; migration; monolayer; new technology; novel strategies; organ regeneration; programs; response; stem cell differentiation; stem cells; success; tumor progression

Project Summary The hierarchical arrangement of cells within tissue plays an important role in determining function. As part of this hierarchical arrangement, different cell types are spatially arranged in contact with one another in a way that transmits important signaling cues that direct a multitude of different functional and dysfunctional cellular responses, such as altered gene expression, migration, metabolite sharing, and survival. A greater understanding of how cell arrangement impacts these behaviors would have important repercussions for a host of developmental processes that include stem cell differentiation, cancer metastasis, scar tissue formation, immunology, and angiogenesis. While the importance of spatially-regulated hierarchical cell arrangements is well established, methods for reproducing this complexity with high precision remain limited. Conventionally, model organisms have informed much of what is understood about these processes, but often do not allow constant direct observation and control. Rapidly evolving 3D printing methods have greatly enhanced our ability to place cells on substrates with libraries of different materials. However, these technologies do not allow one to precisely place individual cells in contact with each other in order to understand how different arrangements drive biological processes in highly heterogenous cell populations. Likewise, techniques that facilitate cell-cell contact placement do not readily enable 3D control with multiple different cell types. This proposal seeks to establish the feasibility of technology that would address this biomedical technological need. Specifically, it evaluates the use of oligonucleotide (short DNA sequences) to precisely control cell placement in an interchangeable and on-the- fly fashion. Aim 1 of this proposal seeks to establish new methods and design rules for dynamically and sequentially adding multiple different cells to a surface with high fidelity and spatial control. Aim 2 seeks to develop a new approach to building spatially controlled 3D cell assemblies using programmable DNA. Completion of this proposal will establish feasibility of this technology for future applications in biomedical studies.

项目摘要 组织内细胞的分层排列在确定功能中起重要作用。作为其中的一部分 层次结构安排，不同的单元格类型在空间上与彼此接触以某种方式 传输引导多种不同功能和功能障碍细胞的重要信号提示 反应，例如改变基因表达，迁移，代谢产物共享和生存。更大 了解细胞排列如何影响这些行为将对宿主产生重要的影响 包括干细胞分化，癌症转移，疤痕组织形成的发育过程， 免疫学和血管生成。虽然空间调节的层次单元布排列的重要性是 良好的，以高精度再现这种复杂性的方法仍然有限。常规上 模型生物已经为这些过程所理解的内容提供了很多信息，但通常不允许 恒定直接观察和控制。快速发展的3D打印方法极大地增强了我们的能力 将细胞放在带有不同材料文库的基材上。但是，这些技术不允许 精确将单个单元格接触，以了解不同的布置如何驱动 高度异质细胞群体中的生物过程。同样，有助于细胞接触的技术 放置不容易启用具有多种不同单元格类型的3D控制。该建议旨在建立 可以满足这种生物医学技术需求的技术的可行性。具体来说，它评估了使用 寡核苷酸（短DNA序列）的精确控制细胞位置 飞行时尚。本提案的目标1旨在为动态建立新的方法和设计规则 依次将多个不同的细胞添加到具有高忠诚度和空间控制的表面。 AIM 2试图 开发一种新方法，使用可编程DNA构建空间控制的3D细胞组件。 该提案的完成将确定该技术在生物医学中的未来应用 研究。