One Way Micropatterns for Self-Assembly and Sorting of Cells

描述（由申请人提供）：精确控制多种细胞类型的定向迁移和空间组织对于维持和工程化组织功能至关重要。生物材料研究的一个主要挑战是设计和制造生物材料，可以引导大量细胞同时自组装生物系统的精度和效率。拟议的研究建立在PI和co-PI最近发现的MANDIP（自然定向持久性的微阵列扩增）的基础上，以指导附着的哺乳动物细胞的远程定向迁移。MANDIP和自由迁移细胞的自然方向持久性的关键是延伸的板状伪足的包膜优先与延伸的细胞体对齐。通过细胞粘附微阵列岛的不对称排列，通过限制板状伪足附着来充当棘轮，MANDIP以压倒性的顺应性施加方向性，同时引导无限数量的细胞独立地在无限距离的任意预设路径上迁移，而无需化学引诱剂外部场或机械操作。本提案的目的是建立MANDIP设计策略的基础，其变革性影响将通过以下具体目标得到证明：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化，目标3：设计一种类似于薄层层析的生物学方法，用于根据细胞的内在运动性分选细胞。 实现这些目标将使MANDIP在促进组织模式形成和作为类似于薄层色谱的普遍存在的低成本细胞分选平台方面的潜力开花结果。 公共卫生相关性：该应用与公共卫生相关，作为一种低成本的细胞分选技术，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。

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.