Imperial College London

Sticky business-imaging intracellular viscosity in dying cells

Imperial College researchers use molecular rotors to measure viscosity in cells via fluorescence lifetime imaging

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Dr Marina Kuimova (Department of Chemistry) has recently published a paper in the first edition of Nature Chemistry showing that the local viscosity of certain areas inside dying cancer cells dramatically increases during light-induced cancer treatment called Photodynamic Therapy (PDT). PDT uses light to activate drugs to produce a very reactive short-lived toxic intermediate, called singlet oxygen, which eradicates malignant cells.

The research provides new images of the physical changes that occur within dying cancer cells. Dr Kuimova and her collaborators from STFC's Rutherford Appleton Laboratory, the University of Oxford and King's College London, are the first research group to reveal real-time maps of intracellular viscosity changing over a period of time during cell death.

A number of important physiological processes depend on intracellular viscosity and changes in viscosity in patients' cells and organs have been linked to disease and malfunction, for example during atherosclerosis or diabetes. Knowing more about these changes could help to better understand how some diseases and their treatments affect physiological function and may also aid in the design of more efficient PDT drugs.

The researchers produced the maps of intracellular viscosity by growing cancer cells in the presence of a novel fluorescent imaging agent, called a molecular rotor which can also act as a PDT drug. In molecular rotors, the speed of intramolecular rotation about a sterically hindered bond is dependent on the viscosity of the surrounding medium. When the viscosity is altered, the change in rotation rate can be detected very quickly by monitoring the change in the fluorescence spectra.

The change in wavelengths emitted during the experiments showed that once the PDT drug was activated the level of viscosity increased dramatically. This is thought to be caused by the toxic oxygen molecules released into the cells. This increased viscosity may also contribute directly to further damage by slowing down signal transduction and intracellular transport. In conclusion, in a dying cell signal transduction from molecule to molecule, and some reactions, which require two reagents to diffuse together, are much slower than normal. However the increased viscosity not only contributes to cell damage, but also slows down the toxic molecules and reduces the efficacy of PDT treatment.

Further research is needed to fully define the interplay between viscosity and cell death and this imaging technique can be used to reveal the changes that occur in real-time in functioning, malfunctioning and dying cells.

Read the press release
Read the Research Highligh comment Nature Chemistry
See Dr Kuimova speak about her work.

Dr Kuimova joined Imperial College in 2005 and is currently an EPSRC Life Sciences Interface Fellow. Her research interests are in elucidation of biologically relevant processes using fluorescence imaging and time-resolved spectroscopy.

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