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Intracellular Microrheology to Measure the Local Mechanical Properties of Live Cells

细胞内微流变学测量活细胞的局部机械特性

基本信息

批准号：
EP/E013988/1
负责人：
Thomas Waigh
金额：
$ 19.09万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FE013988%2F1
关键词：
Intracellular Microrheology Measure Local Mechanical

项目摘要

All living organisms consist of cells; spherical aggregates of biological molecules surrounded by a thin membrane. Viscoelasticity describes the means by which materials store and dissipate energy. Scientists are interested in the viscoelasticity of cells, since it directly relates to their biological functioning and a series of diseases produces altered mechanical behaviours in cells e.g. malaria and heart disease. Previously we have developed a range of techniques for examining the viscoelasticity of purified biological molecules outside the cell. These include tracking the motion of probes spheres with a video camera under a microscope (particle tracking microrheology) and oscillating magnetic particles with a magnetic field, again under an optical microscope (magnetic microrheology). We plan to employ a post-doctoral fellow to investigate the possibilities for intracellular microrheology using the two techniques we have previously developed. The fellow will introduce probes spheres (both polystyrene and magnetic) in to a range of cells. Image analysis techniques will then be applied to study the motion of the probes and the viscoelasticity of the cells will be quantified from point to point. Our group has a range of experience with handling live cells, which are typically difficult to grow without extensive training. In particular we will study smooth muscle cells with the new microrheology techniques, which are important in a range of biological processes including the pumping of blood through veins.The microrheology data will be used to develop new mechanical models for the behaviour of cells. Recent evidence indicates that the proteins most important for the mechanical integrity of the cell (cytoskeletal proteins) have an unusual dynamical behaviour. They act like soft glassy materials and the cell adjusts its elasticity in much the same way that a glassblower fashions a work of glass. Instead of changing the temperature, the cell changes the chemistry of the cytoskeleton and this is the process we hope to study in more detail. Furthermore chemicals will be added to perturb the viscoelasticity of the cells (harden their cytoskeleton) and the effects modelled in terms of the collective statistical behaviour of the molecules contained in the cells.The techniques we develop would have a wide range of medical applications including tissue engineering. Strong links exist between our group and companies that create cellular scaffolding in a range of tissue growth projects.

所有生物都是由细胞组成的；被薄膜包围的生物分子的球形聚集体。粘弹性描述了材料储存和耗散能量的方式。科学家们对细胞的粘弹性很感兴趣，因为它直接关系到细胞的生物功能，而且一系列疾病会改变细胞的机械行为，例如疟疾和心脏病。以前，我们已经开发了一系列技术来检查细胞外纯化的生物分子的粘弹性。这些包括在显微镜下用摄像机跟踪探针球体的运动（颗粒跟踪微流变学）和在磁场下振荡的磁颗粒，再次在光学显微镜下（磁微流变学）。我们计划聘请一名博士后，利用我们之前开发的两种技术来研究细胞内微流变学的可能性。他将在一系列细胞中引入探针球（聚苯乙烯和磁性）。然后，图像分析技术将被应用于研究探针的运动，细胞的粘弹性将被逐点量化。我们的团队在处理活细胞方面有丰富的经验，如果没有广泛的培训，活细胞通常很难生长。特别是我们将用新的微流变学技术研究平滑肌细胞，这在一系列生物过程中是重要的，包括血液通过静脉的泵送。微流变学数据将用于开发细胞行为的新力学模型。最近的证据表明，对细胞机械完整性最重要的蛋白质（细胞骨架蛋白）具有不寻常的动力学行为。它们就像柔软的玻璃材料，细胞调节其弹性的方式与吹玻璃工制作玻璃作品的方式非常相似。细胞不是改变温度，而是改变细胞骨架的化学成分，这是我们希望更详细地研究的过程。此外，将添加化学物质来扰乱细胞的粘弹性（硬化细胞骨架），并根据细胞中所含分子的集体统计行为建立模型。我们开发的技术将有广泛的医学应用，包括组织工程。我们集团和在一系列组织生长项目中制造细胞脚手架的公司之间存在着紧密的联系。