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，使其能够以生物系统的精度和效率引导大量细胞同时自组装。提出的研究建立在PI和co-PI最近发现的MANDIP -自然定向持久性微阵列扩增-指导附着哺乳动物细胞的远距离定向迁移的基础上。MANDIP和自由迁移细胞的自然定向持久性的关键是延长板足的包膜优先与延长的细胞体对齐。通过细胞粘附微阵列岛的不对称排列，通过限制板足附着起到棘轮的作用，MANDIP具有压倒性的适应性，同时引导无限数量的细胞在任意预设的无限距离的路径上独立迁移，而不需要化学吸引剂、外场或机械操作。本提案的目标是为MANDIP设计策略奠定基础，其变革性影响将通过以下具体目标得到证明：目标1：设计单向微模式以指导细胞在生物材料上的定向迁移；目标2：直接多种细胞类型的自组装以模拟肝组织并促进血管形成；目标3：设计薄层色谱的生物模拟物，通过其内在运动性来分选细胞。实现这些目标将实现MANDIP在促进组织模式形成方面的潜力，并作为一种普遍存在的类似薄层色谱的低成本细胞分选平台。

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.