Force Sensing with Nanotubes

用纳米管进行力传感

基本信息

批准号：
8277878
负责人：
Brenda Frances Farrell
金额：
$ 17.02万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8277878
关键词：
Actins Adhesives Advanced Development Binding Biopolymers Breast Carcinoma Carcinoma Cell membrane Cells Characteristics Chemicals Data Diagnostic Neoplasm Staging Embryonic Development Epidermal Growth Factor Epidermal Growth Factor Receptor Epithelial Epithelial Cells F-Actin Filament Filopodia Fluorescence Fluorescence Microscopy Free Energy Goals Growth Factor Growth and Development function Human Image Immune response Invaded Length Life Malignant Neoplasms Mammalian Cell Measurable Measurement Measures Mechanics Mediating Membrane Methodology Methods Microscopy Modeling Molecular Monitor Motor Movement Nanotechnology Nanotubes Natural regeneration Neoplasm Metastasis Organism Pathway interactions Play Preparation Primary Neoplasm Production Proteins Reaction Relative (related person)Research Technics Role Site Solutions Staging Structure Temperature Time Tissues Tongue Traction Tube Work Wound Healing base cancer cell cell growth cell motility cell transformation chemical reaction depolymerization design insight laser tweezer migration monomer mouth squamous cell carcinoma neoplastic cell operation optical traps polymerization receptor rho GTP-Binding Proteins sensor

项目摘要

DESCRIPTION (provided by applicant): Most human malignancies are of epithelial origin. Transformed epithelial cells spread from the primary tumor site and invade surrounding tissues through the production of migratory structures (e.g., filopodia, invadopodia, and lamellapodia). The relative abundance of migratory structures is correlated with the metastatic potential of tumor cells. Migratory structures form by remodeling actin at the leading edge of transformed epithelial cells. Growth factors (e.g., epidermal growth factor, EGF) initiate actin remodeling by targeting their receptors (e.g., epidermal growth factor receptor) on the plasma membrane of transformed cells. Although the EGF pathway is well characterized, we lack experimental evidence to quantify forces that contribute to migration, including adhesive traction, resistive viscous drag, and protrusive forces. This work will focus on protrusive forces that occur at the leading edge of a living cell. They arise when the chemical energy released upon actin polymerization produces a pushing force against the plasma membrane, driven by the greater concentration of monomeric actin in the solution relative to the biopolymer. When an actin bundle is attached to the plasma membrane, depolymerization of F-actin produces a pulling force on the membrane. This reverse chemical reaction is driven by a lower concentration of monomer in the bulk relative to the biopolymer. Experimental measurements of the magnitude and time course of the pushing force in living cells are lacking and there are no measurements of the pulling force arising from the depolymerization of F-actin. The goal of this work is to determine the time course and magnitude of the pushing and pulling forces at the fast-growing end of an F-actin bundle. We will use the membrane as a sensor to determine the force at the motor-level in cancer cells. We will stimulate transformed epithelial cells to form migratory structures by EGF or with active effectors within the EGF pathway. We will use optical tweezers to measure the force, fluorescence microscopy to image F- actin, and develop methodology to measure both simultaneously. This work will provide a functional model of the actin motor at a leading edge of transformed epithelial cells, and advance the field in understanding cell migration during the invasive stage of cancer by providing measurements of the protrusive force at one leading edge. It will provide a quantitative experimental method to investigate the transduction machinery of this chemical motor, and fundamental insight into the integrated operations of the cell membrane and actin motor. This work will provide a basis to design force sensors for applications in nanotechnology.

描述（由申请人提供）：大多数人类恶性肿瘤都是上皮的。转化的上皮细胞从原发性肿瘤部位扩散，并通过产生迁移结构（例如丝状菌，Invadopodia和Lamellapodia）侵入周围的组织。迁移结构的相对丰度与肿瘤细胞的转移潜力相关。通过在转化的上皮细胞的前缘重塑肌动蛋白来形成迁移结构。生长因子（例如表皮生长因子，EGF）通过将其受体（例如表皮生长因子受体）靶向转化细胞的质膜来启动肌动蛋白重塑。尽管EGF途径的表征很好，但我们缺乏实验证据来量化有助于迁移的力，包括粘合性牵引力，电阻粘性阻力和突出力。这项工作将集中在活细胞前缘发生的突出力。当肌动蛋白聚合释放的化学能在溶液中相对于生物聚合物的溶液中较高浓度的元素驱动时，它们会产生推动力。当肌动蛋白束附着在质膜上时，F-肌动蛋白的解聚会在膜上产生拉力。这种反向化学反应是由相对于生物聚合物的大块中浓度较低的单体驱动的。缺乏活细胞推动力的大小和时间过程的实验测量，并且没有F-肌动蛋白解聚作用引起的拉力的测量。这项工作的目的是确定在F-肌动蛋白束的快速增长端的推动力和拉力的时间过程和幅度。我们将使用膜作为传感器来确定癌细胞中运动水平的力。我们将刺激转化的上皮细胞以EGF或EGF途径内的活性效应子形成迁移结构。我们将使用光学镊子测量力，荧光显微镜来形象f-肌动蛋白，并开发同时测量两者的方法。这项工作将在转化的上皮细胞的前缘提供肌动蛋白电动机的功能模型，并通过在一个前缘的一个前缘进行测量，从而在癌症的侵入性阶段中促进了在癌症侵入性阶段迁移的领域。它将提供一种定量的实验方法，以研究该化学电动机的转导机械，并对细胞膜和肌动蛋白运动的综合操作的基本见解。这项工作将为设计纳米技术应用的力传感器提供基础。