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: 10471175
• 负责人: Brian R Meckes
• 金额: $ 17.28万
• 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/10471175
• 关键词: 3-Dimensional; 3D Print; Address; Animal Model; Area; Artificial tissue; 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.

项目概要 组织内细胞的层次排列在决定功能方面起着重要作用。作为本次活动的一部分 分层排列，不同的细胞类型在空间上排列成彼此接触的方式： 传递重要的信号线索，指导多种不同功能和功能失调的细胞 反应，例如改变基因表达、迁移、代谢物共享和生存。一个更大的 了解细胞排列如何影响这些行为将对宿主产生重要影响 发育过程，包括干细胞分化、癌症转移、疤痕组织形成、 免疫学和血管生成。虽然空间调节的分层细胞排列的重要性是 虽然已经成熟，但高精度再现这种复杂性的方法仍然有限。按照惯例， 模式生物已经告知了人们对这些过程的大部分了解，但通常不允许 持续的直接观察和控制。快速发展的3D打印方法极大地增强了我们的能力 将细胞放置在具有不同材料库的基底上。然而，这些技术不允许人们 精确地将单个细胞彼此接触，以了解不同的排列如何驱动 高度异质细胞群中的生物过程。同样，促进细胞与细胞接触的技术 放置不容易实现对多种不同细胞类型的 3D 控制。该提案旨在建立 满足这种生物医学技术需求的技术的可行性。具体来说，它评估使用 寡核苷酸（短 DNA 序列），以精确控制细胞在可互换和现场放置 飞扬时尚。该提案的目标 1 旨在建立新的方法和设计规则，以实现动态和 以高保真度和空间控制顺序将多个不同的细胞添加到表面。目标 2 旨在 开发一种使用可编程 DNA 构建空间控制 3D 细胞组件的新方法。 该提案的完成将确定该技术未来在生物医学领域应用的可行性 研究。