Developing GHz Acoustic Methods for Imaging and Measuring the Mechanical Properties of Individual Cells

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Cells migrate by attaching themselves to their surroundings and generating traction forces by rearranging their internal structure. The effectiveness of these tractions depend on the relative rigidity of the cells internal structure (its cytoskeleton) and that of the surrounding material. This can be probed by measuring the elastic properties (stiffness) of a cell and how these properties vary across the cell during migration. There is some evidence that as cells transform from the normal to the cancerous state, their stifness is reduced, and as these cells become progressively more invasive the stiffness is reduced further. Thus by developing methods to probe the mechanical properties of cells we can investigate some fundamental aspects of cell biology and cancer cell biology. In this proposal we will investigate the use of ultra-high frequency acoustic imaging to study the mechanical properties of individual cells. In an acoustic microscope specimens are imaged by acoustic waves in the frequency range 100 MHz - 1 GHz. Image contrast occurs from local differences in the speed of sound, which in turn is a function of the elastic stiffness of the material being imaged. Thus, by measuring the contrast of images of cells at a range of acoustic frequencies it is possible to determine local mechanical properties with a spatial resolution of around 1 micron. However, for this technique to be applicable to the study of the biochemical and physical processes that occur during cell migration, it is necessary to further develop the technique to allow the rapid acquisition of data through images taken every few seconds. The technique will be demonstrated through the investigation of the migration of cell lines that can be controlled by altering one of the proteins used during the migration process thus allowing us to compare cells that migrate rapidly with those that are more static. We will also work in collabnoration with Cancer Research UK who will provide examples of cell lines of known invasive capability for us to characterize their mechanical properties.