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The Secretsof Protein Diffusion
March 27, 2013   
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The rate at which chemical processes take place in cells depends on the speed of movement (diffusion) of molecules needed for a given reaction. Using a versatile method developed at the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw, researchers are now able to predict the diffusion coefficients of all proteins in Escherichia coli bacteria.

To understand the chemical foundations of life, scientists need to be familiar with the rate at which chemical reactions occur in cells. The speed of these reactions depends on how fast the molecules taking part in the reactions move in the cytoplasm. A research team led by Prof. Robert Hołyst at the Institute of Physical Chemistry has managed to determine that.

The research has been supported by grants from the National Science Center and the Ministry of Science and Higher Education as well as by programs run by the Foundation for Polish Science. The results of the research, which focused on the rate of diffusion of protein molecules in the Escherichia coli cytoplasm, have been published in the Bioinformatics journal.

“The viscosity inside mammalian cells is relatively low, only 60 times higher than that of water. But bacteria are considerably smaller, everything is more crowded. The macroscopic viscosity there is up to 26,000 times higher than that of water,” says the Institute of Physical Chemistry’s Tomasz Kalwarczyk, Ph.D.

Earlier research by Hołyst’s team found that the viscosity experienced by molecules is not only medium, i.e. solvent, dependent, but also depends on the size and shape of molecules. Therefore, in the same medium, molecules differing in shape and size can experience very low viscosity (nanoviscosity) or macroscopic viscosity up to several thousand times higher. Previous methods for predicting diffusion coefficients in cytoplasm did not account for that effect.

The experimental determination of the diffusion rates of chemical compounds in bacterial cells is time-consuming and difficult. As a result, diffusion coefficients have only been measured for a limited number of compounds in only some bacterial cells. That’s why the researchers from the institute have developed a method for predicting diffusion coefficients for various compounds and media. For that purpose they used their own formulae, accounting for nanoviscosity and macroscopic viscosity, and several dozen diffusion coefficients of macromolecules in Escherichia coli bacteria taken from the literature. On this basis, they constructed a scale-dependent viscosity reference curve that could be used to determine the diffusion coefficients of the remaining compounds.

The database constructed at the institute contains the diffusion coefficients of all known proteins occurring in Escherichia coli. This means over 6,000 macromolecules, with about 4,300 gene-expressed amino acid chains and their various, often multiple combinations (polymers), created by both the same chains (homomers) and different amino acids (heteromers).

The institute’s Marcin Tabaka, Ph.D., said, “Because of the easy access to the literature data, we created a database only for proteins occurring in Escherichia coli. However, our method could be adapted for virtually any cell and every molecule, for instance for determining the diffusion coefficients of sugars in mammalian cells.”
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