Cells quake. In somewhat the same way that seismologists use the vibrations of planet Earth to characterize its deep structure, scientists have discovered a way to use vibrations within cells to identify their mechanical properties. Thus was born the field of cell seismology.
"We developed a unique technique to map, on a scale of milliseconds, the elasticity of the components inside a cell," said Guy Cloutier, a researcher at the University of Montreal Hospital Research Centre (CRCHUM) and professor at Université de Montréal. "This opens up a whole new field of research in mechanobiology to study the dynamics of displacements inside cells and understand the impact of these forces on diseases and treatments."
The technology, called "cell quake elastography", is presented in an article published today in the Proceedings of the National Academy of Sciences(PNAS).
Elasticity is a fundamental property of cells, related to the anatomy, function and pathological state of cells and tissues. A cancerous tumour becomes rigid. Atherosclerosis and vascular aneurysms start with a loss of elasticity in the cells and arteries. Endothelial cells release transmitters that cause the vasoconstriction or vasodilation of blood vessels, depending on the mechanical shear conditions associated with vessel flow and geometry.
"Until now, it has been difficult to measure the mechanical changes that continuously occur in cells," explained Pol Grasland-Mongrain, a post-doctoral trainee in Guy Cloutier's laboratory and the principal author of the study. "With current techniques, based on cell deformation, atomic force microscopy and Brillouin scattering, it can take several dozen minutes to measure elasticity. For certain applications, this is much too slow because thousands of events can occur in a cell, such as ion transfers, neuron stimulations and cell death. These phenomena would be easier to track if we were able to measure the mechanical properties of cells.
With simple equipment consisting of a standard microscope, micropipettes and a high-speed camera, the researchers developed a revolutionary method of observing, in real time, the displacements and forces present in mouse oocytes. According to Greg FitzHarris, a researcher at the CRCHUM, Université de Montréal professor and one of the project's collaborators, "with this new cellular imaging method, we will be able to investigate new mechanisms involved in cell division during embryo formation".
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Bridging physics, engineering, and microbiology, researchers at MIT have measured the frequency at which red blood cells vibrate and have shown that those frequencies reflect the health of the cells. The research could lead to better medical diagnostics.
Vibrant cells:MIT’s Michael Feld and Subra Suresh, with the aid of a technique developed in Feld’s lab, were able to image the vibrations of the membrane of a blood cell infected with the malaria parasite (top). Feld’s technique also provided images of the interior of the cells (bottom), allowing the researchers to correlate the cells’ vibrational frequencies with the progress of the disease.
The work was performed in collaboration between MIT physicist Michael Feld and Subra Suresh, dean of MIT’s school of engineering and a materials scientist. Feld heads MIT’s Laser Biomedical Research Center, which has developed an imaging technique that can create three-dimensional images of living cells. Suresh’s laboratory has conducted experiments to measure things like the stiffness of red blood cells infected by malaria parasites.
A red blood cell has electrical, chemical, and biological activity taking place inside it, which causes nanoscale vibrations at its surface. To measure the cells’ vibrational frequencies, the researchers combined Feld’s imaging technique with diffraction phase microscopy, in which a laser beam that passes through a cell rejoins a reference beam that does not, creating a distinctive interference pattern. To establish the connection between the cells’ vibration and their health, the researchers used Feld’s technique to create three-dimensional images of a malarial parasite inside a red blood cell. Vibrating cell membranes move mere nanometers at a time, and those movements take place in microseconds–millionths of a second. To capture the data from the laser beam passing through the cells, the researchers used Feld’s imaging technique, which stitches multiple images together into a composite. The technique is a species of tomography, the principle that underlies computed-tomography (CT) scans.
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