The effect of macromolecular crowding on mobility of biomolecules, association kinetics, and gene expression in living cells

Abstract

We discuss a quantitative influence of macromolecular crowding on biological processes: motion, bimolecular reactions, and gene expression in prokaryotic and eukaryotic cells. We present scaling laws relating diffusion coefficient of an object moving in a cytoplasm of cells to a size of this object and degree of crowding. Such description leads to the notion of the length scale dependent viscosity characteristic for all living cells. We present an application of the length-scale dependent viscosity model to the description of motion in the cytoplasm of both eukaryotic and prokaryotic living cells. We compare the model with all recent data on diffusion of nanoscopic objects in HeLa, and E. coli cells. Additionally a description of the mobility of molecules in cell nucleus is presented. Finally we discuss the influence of crowding on the bimolecular association rates and gene expression in living cells.

Motion of nanoprobes in complex liquids within the framework of the length-scale dependent viscosity model

“…The models include those 35 based on the obstruction effect [5-8], on hydrodynamic theories [9][10][11][12][13][14][15][16], on the free volume theory [17][18][19][20][21][22][23], and on anomalous diffusion [24,25]. The motion of bigger probes (r p in the range from fractions to several micrometers), is usually described in terms of microrheology [26,27].…”

“…A strong advantage 45 of this model is that it can be applied to many types of complex liquids including polymer [29][30][31][32][33], micellar [30,34], or colloidal solutions [2], or the cytoplasm of mammalian [30,35] or bacterial [35][36][37][38] cells.…”

“…The rotational friction experienced by a moving probe 545 couples with the translational friction thus effectively increasing the experienced viscosity [35]. The later example shows that an additional work needs to be done in order to investigate A C C E P T E D M A N U S C R I P T…”

“…The model can be applied to a wide 530 range of complex liquids: polymers [29,30,32,33], micelles [30], colloids [2] or the cytoplasm of living cells [30,[35][36][37][38].…”

Effect of crowding on protein-protein association in diffusion-limited regime

“…Understanding the physical principles governing association mechanisms and rate constants and furthermore, realistically modeling them, are crucial to study the relationship between the cellular structure and function. To facilitate experimental studies in vitro, synthetic polymers such as polyethylene glycol (PEG), ficoll, dextran, and poly(vinyl alcohol), are commonly used as a means to mimic molecular crowding in the cell [3,4,5]. For instance, crowding effects on protein folding, binding, oligomerization, and protein-protein association have been widely investigated by using polymer solutions [6,7,5].…”