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

基本信息

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

项目摘要

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.

CBET-0707969冬季，申请人使用磁性纳米颗粒（即超脑磁铁氧化铁纳米颗粒（SPIONS））为细胞的物理操作创建细胞内纳米探针。 SPION是机械细胞纳米探针的出色候选材料，因为它们可以用作物理执行器，从而产生对磁场的受控的，研究人员触发的Force。以前，已封装在磁性中的SPION已用于检查细胞对细胞外力的反应。疗法表明，细胞骨架是一种负责细胞机械整合性的生物聚合物网络，是可以影响许多细胞功能的精细机械传输系统的一部分。但是，这些研究使用了大颗粒，近的一半是细胞的大小，通过细胞外细胞表面受体与细胞骨架进行了直接的界面。尽管已经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进行递送。颗粒仍然被困在内体中，无法与胞质结构相互作用。因此，操纵细胞骨架的潜力直接保持不开发。在该提案中，研究者将采用SPIONS作为物理细胞内纳米探针，以直接的，靶向肌动蛋白细胞骨架的靶向操作。作为模型系统，将探讨成纤维细胞迁移中的靶向性和非靶向细胞骨架操纵的作用。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。使用纳米颗粒来控制细胞迁移的能力可能对发育生物学具有重大影响，并为慢性或灾难性伤口护理提供新的治疗途径。