One Way Micropatterns for Self-Assembly and Sorting of Cells

用于细胞自组装和分选的单向微图案

• 批准号: 7767586
• 负责人: CHIA-CHI HO
• 金额: $ 35.02万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7767586
• 关键词: Actins; Address; Adhesions; Adhesives; Area; Automobiles; Biocompatible Materials; Biological; Biomaterials Research; Cell Count; Cell Line; Cell Migration Pathway; Cell Separation; Cell Shape; Cell physiology; Cells; Chemicals; Chemotactic Factors; Collaborations; Complex; Cues; Cytoskeleton; Family; Foundations; Funding; GTP-Binding Proteins; Hepatic Stellate Cell; Hepatocyte; Hepatocyte Growth Factor; In Vitro; Island; Lead; Liver; Location; Mammalian Cell; Mechanics; Molecular; Molecular Genetics; Movement; Natural regeneration; Nerve Regeneration; Neurons; Organ; Pattern; Pattern Formation; Positioning Attribute; Process; Public Health; Receptor Protein-Tyrosine Kinases; Regulation; Research; Resolution; Signal Pathway; Signal Transduction; Structure; Techniques; Technology; Thin Layer Chromatography; Time; Tissue Engineering; Tissues; Vascularization; analog; base; biological research; biological systems; cell assembly; cell growth; cell motility; cell type; cost; design; directional cell; disease diagnosis; in vivo; migration; multidisciplinary; neuronal cell body; next generation; polymerization; public health relevance; response; rho; scaffold; self assembly; shear stress; trafficking

DESCRIPTION (provided by applicant): Precise control of directional migration and spatial organization of multiple cell types is critical to maintaining and engineering tissue function. A major challenge in biomaterials research is the design and fabrication of biomaterials that can guide the simultaneous self-assembly of large number of cells with the precision and efficiency of biological systems. The proposed research builds on the PI and co-PI's recent discovery of MANDIP - Microarray Amplification of Natural Directional Persistence - to guide the long-range directional migration of attached mammalian cells. Key to MANDIP and the natural directional persistence of freely migrating cells is that the envelope of extended lamellipodia is preferentially aligned to the extended cell body. Through an asymmetric arrangement of cell adhesive microarray islands that acts as a ratchet by restricting lamellipodia attachment, MANDIP imposes directionality with overwhelming compliance, guiding simultaneously the migration of unlimited number of cells independently over arbitrary preset paths of unlimited distance without chemoattractants external fields, or mechanical manipulation. The objective of this proposal is to establish a foundation of MANDIP design strategies whose transformative impact will be demonstrated through the following specific aims: Aim 1: Design one-way micropatterns to guide the directional migration of cells on biomaterials, Aim 2: Direct self-assembly of multiple cell types to mimic liver tissue and promote vascularization, Aim 3: Devise a biological analogue of thin-layer chromatography for sorting cells by their intrinsic motility. Accomplishing these aims will bring to fruition MANDIP's potential in promoting tissue pattern formation and as a ubiquitous low-cost cell-sorting platform analogous to thin layer chromatography. PUBLIC HEALTH RELEVANCE: The application is relevant to public health as a low-cost cell sorting technology for rapid screening/purification of cells or diagnosis of diseases related to cell motility and can be applied to engineer tissues by 3D scaffolds that direct migration of multiple cell types.

描述(申请人提供)：精确控制多种细胞类型的定向迁移和空间组织是维持和设计组织功能的关键。生物材料研究中的一个主要挑战是设计和制造能够以生物系统的精度和效率引导大量细胞同时自组装的生物材料。这项拟议的研究建立在PI和Co-PI最近发现的Mandip-微阵列自然定向持久性放大-以指导附着的哺乳动物细胞的远程定向迁移的基础上。Mandip和自由迁移细胞的自然定向持久性的关键是扩展的片状脂体的包膜优先与扩展的细胞体对齐。通过细胞粘附性微阵列岛的不对称排列，通过限制片状脂质体的附着充当棘轮，Mandip以压倒一切的顺应性施加方向性，同时引导无限数量的细胞在没有化学吸引剂外场或机械操作的情况下，在不限距离的任意预设路径上独立迁移。这项建议的目的是建立Mandip设计策略的基础，其变革性的影响将通过以下具体目标来展示：目标1：设计单向微图案以引导细胞在生物材料上的定向迁移，目标2：多种细胞类型的直接自组装以模拟肝组织并促进血管形成，目标3：设计一种薄层色谱的生物类似物，用于根据细胞的内在运动性对细胞进行分选。实现这些目标将使曼迪普在促进组织图案形成和作为类似于薄层色谱的无处不在的低成本细胞分类平台方面的潜力发挥出来。 与公共健康相关：作为一种低成本的细胞分选技术，该应用程序与公共健康相关，用于快速筛选/纯化细胞或诊断与细胞运动相关的疾病，并可通过引导多种细胞类型迁移的3D支架应用于工程组织。