Intracellular Microrheology to Measure the Local Mechanical Properties of Live Cells

所有的生物体都是由细胞组成的;细胞是由一层薄薄的膜所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。科学家对细胞的粘弹性感兴趣，因为它直接关系到细胞的生物功能，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的技术，用于检查细胞外的纯化生物分子的粘弹性。这些方法包括在显微镜下用摄像机跟踪探针球的运动（粒子跟踪微流变学）和在光学显微镜下用磁场振荡磁性粒子（磁性微流变学）。我们计划聘请一名博士后研究员使用我们以前开发的两种技术来研究细胞内微观流变学的可能性。这位研究员将把探针球（聚苯乙烯和磁性）引入一系列细胞中。然后应用图像分析技术研究探针的运动，并逐点量化细胞的粘弹性。我们的团队在处理活细胞方面有着丰富的经验，这些活细胞通常在没有广泛培训的情况下很难生长。特别是，我们将研究平滑肌细胞与新的微观流变学技术，这是重要的一系列生物过程，包括泵血通过静脉。微观流变学数据将用于开发新的力学模型的细胞的行为。最近的证据表明，对细胞的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大致相同。细胞改变的不是温度，而是细胞骨架的化学性质，这是我们希望更详细研究的过程。此外，还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来模拟这些效应。我们开发的技术将具有广泛的医学应用，包括组织工程。我们的团队与在一系列组织生长项目中创建细胞支架的公司之间存在着密切的联系。

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.