High-throughput intracellular microrheology: a new tool for cancer research

高通量细胞内微流变学：癌症研究的新工具

基本信息

批准号：
8079080
负责人：
Denis Wirtz
金额：
$ 20.11万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-08 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8079080
关键词：
Actins Advanced Malignant Neoplasm Aftercare Atomic Force Microscopy Ballistics Biological Assay Biomedical Engineering Biophysics Body Fluids Cancer Biology Carcinoma Cell Adhesion Cell Density Cell Line Cell membrane Cell-Cell Adhesion Cells Cellular biology Chemicals Chemistry Chemotherapy-Oncologic Procedure Clinical Collaborations Complement Complex Computers Cultured Tumor Cells Cytoplasm Cytoskeleton Detection Development Devices Diagnosis Diagnostic Discipline of obstetrics Disease Disease model Doctor of Philosophy Early Diagnosis Elasticity Engineering Epithelial Cells Equilibrium Etiology Evaluation Fluorescence Microscopy Growth Factor Gynecology Harvest Hospitals Immunofluorescence Immunologic Individual Injection of therapeutic agent Life Liquid substance Malignant Epithelial Cell Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Measurement Measures Mechanics Medicine Methods Microscope Molecular Morbidity - disease rate Nature Neoplasm Metastasis Normal Cell Operative Surgical Procedures Ovarian Ovarian Carcinoma Ovarian Serous Adenocarcinoma Pathology Patients Pharmaceutical Preparations Phenotype Positioning Attribute Property Recurrence Reproducibility Research Research Personnel Resolution Schools Serous Shapes Specimen Staging Stretching Students Surface Survival Rate Symptoms Testing Therapeutic Time Tumor Cell Invasion Tumor Debulking Viscosity Woman Work anticancer research base cancer cell cell injury cell motility cellular engineering chemotherapeutic agent chemotherapy density design high risk immortalized cell improved instrument medical schools migration mortality mouse model oncology particle pressure prevent prototype response tool wound

项目摘要

DESCRIPTION (provided by applicant): Cancer mortality and morbidity are critically related to tumor invasion and metastasis in which the molecular mechanisms are poorly understood. Until their etiology is better revealed, attempts to develop new cancer therapeutics would remain empirical. Cell motility, which drives cancer metastasis, involves dynamic and regulated re-arrangements of the cytoskeleton. Our work and that of several other groups have shown that cytoskeleton phenotypes are typically accompanied by drastic changes in the viscoelastic properties of the cytoskeleton, which in turn modulate the ability of the cytoskeleton to generate net pushing forces at the leading edge and allow the cell to change its shape. Changes in cell mechanical properties have long been predicted to correlate with metastatic potential. However, current cell-mechanics approaches suffer from serious drawbacks - including time of measurement, lack of multiplexing, ambiguity of measurements - which prevent a direct test of this important hypothesis. The objective of this study is to: develop a highly-optimized high-throughput ballistic injection nanorheology (htBIN) technological platform to measure the micromechanical properties in cancer cells rapidly (< 30 seconds per cell) and reliably, and to assess these biophysical properties as a function of cell migration and invasion by comparing ovarian cancer cells of low and high invasive nature to normal cells, all obtained from patients at the Johns Hopkins Hospital. The proposed instrument, which is based on multiple-particle microrheology, presents key advantages over current approaches to cell mechanics. Our device will serve as a new tool for cancer research to study cell mechanics in the context of cancer cell migration and adhesion, and may ultimately serve as a diagnostic tool for patients who are at high risk for ovarian cancer, complementing more conventional biomolecular markers of cancer in a clinical setting While our proposed approach to cell mechanics is a priori applicable to detect intracellular mechanical differences in any type of cancer cells, a primary focus of this project is ovarian cancer. Ovarian cancer was selected as the disease model in this study because it represents one of the most aggressive cancers in women.

描述（由申请人提供）：癌症的死亡率和发病率与肿瘤侵袭和转移密切相关，其中分子机制知之甚少。在更好地揭示其病因之前，开发新的癌症治疗剂的尝试将仍然是经验性的。驱动癌症转移的细胞运动涉及细胞骨架的动态和调节的重新分配。我们的工作和其他几个组的工作表明，细胞骨架表型通常伴随着细胞骨架的粘弹性特性的急剧变化，这又调节了细胞骨架在领先边缘产生净推力的能力，并允许细胞的形状改变其形状。长期以来，细胞机械性能的变化与转移潜力相关。然而，当前的细胞力学方法遭受了严重的缺点 - 包括测量时间，缺乏多路复用，测量的模棱两可 - 这阻止了对这一重要假设的直接检验。这项研究的目的是：开发一种高度优化的高通量弹道注射纳米流行病学（HTBIN）技术平台，以迅速测量癌细胞中的微机械性能（每个细胞<30秒），并可靠地评估这些生物物理特性，以评估这些生物物理性特性，从而通过比较细胞的功能和较高的ovarian collist of of ovarian collaiss of ovarian癌症细胞，并具有较高的ovarian癌症细胞，并具有较高的性质。霍普金斯医院。所提出的仪器基于多粒子微流变学，比当前的细胞力学方法具有关键优势。我们的设备将作为癌症研究的新工具，在癌细胞迁移和粘附的背景下研究细胞力学，并最终可以作为患有卵巢癌高风险的患者的诊断工具，补充癌症的更常规生物分子标记在临床上的传统生物分子标记，而我们提出的细胞力学方法是对这种癌细胞差异的先验性癌症差异。卵巢癌被选为本研究的疾病模型，因为它代表了女性最具侵略性的癌症之一。