New insight into viscosity and the cytoplasm of cancer cells

The researchers from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) have described in a physically consistent manner the changes in viscosity as measured in various solutions and experienced by probes with size varying from a nano to a macro scale. Their findings have just been published by the journal Nano Letters. "We improved our earlier formulae and conclusions to successfully apply them to a larger number of systems, including the first description of the cytoplasm viscosity in cancer cells," says Prof. Robert Hołyst from the IPC PAS.

The very first scientific publication to address the viscosity of complex fluids was a paper by Albert Einstein from 1906. In the time that followed intriguing evidence has been presented with regard to the cytoplasm viscosity in cells. This experimental evidence indicated that in spite of a high cytoplasm viscosity the mobility of small proteins in the cytoplasm is high -- many orders of magnitude higher than the Stokes-Sutherland-Einstein formula would imply.

The researchers from the IPC PAS managed to describe the viscosity changes using one phenomenological formula containing coefficients of the same physical nature. The coefficients give a description for both the fluid medium (filled, for instance, with a network of long-chained polymers or clusters of molecules) and the probe (e.g., protein molecule) moving in the medium. The new formula is of universal importance and can be used for probes from a fraction of nanometer up to centimeters in size. The relationships found are generally valid for various types of fluids including solutions with elastic microscopic structure (e.g., polymer networks in various solvents) and microscopically rigid systems (e.g., composed of elongated aggregates of molecules -- micelles).

In the Nano Letters report the researchers from the IPC PAS applied the new formula to describe the mobility of DNA fragments and other probes in mouse muscle cells (Swiss 3T3) and human cancer cells (HeLa). "We managed to show that the fluid viscosity in the cell depends actually not only on the intracellular structure but also on the size of the probe used in viscosity measurement," says Tomasz Kalwarczyk, a PhD student from the IPC PAS.

The researchers from the IPC PAS measured the so called correlation length that in the cytoplasm of the Swiss 3T3 cells was 7 nanometers (a billionth part of a meter), and in the HeLa cells -- 5 nm. The correlation length is a limiting parameter for viscosity -- the proteins smaller in size than the correlation length move freely in the cell. Another limiting parameter determined in the study was the hydrodynamic radius of the objects the fluid is made of. This is also an essential parameter, as the probes larger than the hydrodynamic radius experience macroscopic viscosity (the probes larger than the correlation length but smaller than the hydrodynamic radius experience viscosity that increases dramatically with probe size). It turned out that in the HeLa cells, the macroscopic viscosity was experienced by probes larger than 350 nm, whereas in the Swiss 3T3 cells the threshold was 120 nm only. "Our research resulted in a novel method to characterise cell structure -- by measuring the viscosity of the cytoplasm," stresses Kalwarczyk.

The outcome of the research presented by the scientists from the ICP PAS will allow to estimate better the migration time of drugs introduced in cells, and will be also applied in nanotechnologies, for instance in fabrication of nanoparticles with micellar solutions. The findings of the study are also of significant importance for advanced measurement methods, such as dynamic light scattering, that allow to analyse suspensions of molecules by their sizes. If the dependence of viscosity on the size of the viscosity probe used is not taken into account, the results of the measurements can be affected by significant errors.

The research on viscosity at the IPC PAS is co-financed by the EU "European Regional Development Fund" under a TEAM grant of the Foundation for Polish Science.