NER: Intracellular Nanoprobes for Physical Manipulation of Cells

NER：用于细胞物理操作的细胞内纳米探针

• 批准号: 0707969
• 负责人: Jessica Winter
• 金额: $ 12.97万
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0707969&HistoricalAwards=false
• 关键词: NER; Intracellular; Nanoprobes; Physical; Manipulation

CBET-0707969 Winter The applicant is creating intracellular nanoprobes for the physical manipulationof cells using magnetic nanoparticles (i.e., supraparamagnetic iron oxide nanoparticles(SPIONs)). SPIONs are excellent candidate materials for mechanical cellular nanoprobesbecause they can serve as physical actuators, producing a controlled, investigator-triggeredforce in response to a magnetic field. Previously, SPIONs encapsulated in magneticmicrospheres have been used to examine the response of cells to extracellular force. Thesestudies demonstrated that the cytoskeleton, a biopolymer network responsible for the mechanicalintegrity of cells, is part of an elaborate mechanotransduction system that can influence manycell functions. However, these studies use large particles, nearly half the size of a cell, whichindirectly interface with the cytoskeleton through extracellular cell surface receptors. Althoughsome attempts have been made to use smaller SPIONs inside a cell, these methods rely onparticle endocytosis for delivery. Particles remain trapped in endosomes, unable to interact withcytoplasmic structures. Thus, the potential to manipulate the cytoskeleton directly remainslargely untapped.In this proposal the investigator will employ SPIONs as physical intracellular nanoprobes for direct, targeted manipulation of the actin cytoskeleton. As a model system, the roleof targeted versus untargeted cytoskeletal manipulation in fibroblast cell migration will be explored. Cell migration is a critical factor in embryonic development, nerve regeneration, tumor metastasis and wound healing repair. The ability to control cell migration using nanoparticles could have substantial implications for developmental biology and provide new therapeutic avenues for chronic or catastrophic wound care.

申请人正在创建细胞内纳米探针，用于使用磁性纳米颗粒（即超顺磁性氧化铁纳米颗粒（SPIONs））对细胞进行物理操作。SPIONs是机械细胞纳米探针的优秀候选材料，因为它们可以作为物理致动器，在响应磁场时产生可控的、探针触发的力。以前，包裹在磁性微球中的SPIONs已被用于检测细胞对细胞外力的反应。这些研究表明，细胞骨架是一个生物聚合物网络，负责细胞的机械完整性，是一个复杂的机械转导系统的一部分，可以影响许多细胞功能。然而，这些研究使用的是大颗粒，几乎是细胞大小的一半，通过细胞外细胞表面受体直接与细胞骨架接触。尽管有人尝试在细胞内使用较小的spion，但这些方法依赖于粒子内吞作用来传递。颗粒被困在核内体中，无法与细胞质结构相互作用。因此，直接操纵细胞骨架的潜力在很大程度上仍未开发。在这个提议中，研究者将使用SPIONs作为物理细胞内纳米探针直接，有针对性地操纵肌动蛋白细胞骨架。作为一个模型系统，靶向与非靶向细胞骨架操作在成纤维细胞迁移中的作用将被探索。细胞迁移是胚胎发育、神经再生、肿瘤转移和伤口愈合修复的关键因素。利用纳米颗粒控制细胞迁移的能力可能对发育生物学具有重大意义，并为慢性或灾难性伤口护理提供新的治疗途径。