Intracellular Microrheology to Measure the Local Mechanical Properties of Live Cells

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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.