Biologistics and biochemistry in a crowded environment are two emerging interdisciplinary fields of science. They provide quantitative analysis of mobility of proteins and their interactions involved in gene expression and regulation. I will discuss the mobility of small ligands, proteins and plasmids in cytoplasm of E.coli HeLa and Swiss 3T3 cells [1, 4] and in complex liquids [1-3]. I will explain why proteins move so fast in seemingly highly crowded environments (e.g. cell nucleus, mitochondria or cytoplasm of bacteria). Most proteins (of sizes below 5 nm) have the same mobility in the cytoplasm of eukaryotic cells as in water [1]. Therefore their association rate does not differ much from the one measured in vitro (in a buffer) [5, 6]. For the first time such association of two freely diffusing proteins in a cytoplasm of HeLa cell was measured in 2012 [6]. I will also provide specific-site searching time for 180 known transcription factors in E.coli and discuss the results from perspective of facilitated target location and mobility in living cells [4, 7, 8, 9, 10]. Finally I will give a simple prescription for quantitative analysis of interactions between proteins and macrostructures inside living cells based on their mobility data [10].

References:

[1] T. Kalwarczyk et al, Comparative Analysis of Viscosity of Complex Liquids and Cytoplasm of Mammalian Cells at the Nanoscale Nano Letters 2011, 11, 2157
[2] R. Holyst et al, Scaling form of viscosity at all length-scales in poly(ethylene glycol) solutions studied by fluorescence correlation spectroscopy and capillary electrophoresis Phys. Chem. Chem. Phys. 2009, 11, 9025-9032.
[3] J. Szymanski et al, Diffusion and Viscosity in a Crowded Environment: from Nano- to Macroscale J. Phys. Chem. B 2006, 110, 25593-25597.
[4] T. Kalwarczyk, M. Tabaka, R. Hołyst, Biologistics-diffusion coefficients for the complete proteome of E.coli Bioinformatics 2012, 28, 2971-8.
[5] M. Tabaka, L. Sun, T. Kalwarczyk and R. Holyst, Implications of macromolecular crowding for protein-protein association kinetics in the cytoplasm of living cells Soft Matter 2013, 9, 4386.
[6] Y. Phillip, V. Kiss, G. Schreiber, Protein-binding dynamics imaged in a living cell PNAS 2012, 109, 1461-1466.
[7] P. Hammar et al, The lac Repressor Displays Facilitated Diffusion in Living Cells Science 2012, 336, 1595.
[8] J. Elf, G-W. Li, X.S. Xie, Probing transcription factor dynamics at the single-molecule level in a living cell Science 2007, 316, 1191.
[9] P. Blainey et al, Nonspecifically bound proteins spin while diffusing along DNA Nature Structural & Molecular Biology 2009, 16, 1224.
[10] M. Tabaka, T. Kalwarczyk, R. Hołyst, Quantitative influence of macromolecular crowding on gene regulation kinetics Nucleic Acids Research 2014 42 (2): 727-738.

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