Macromolecular Crowding Regulates the Gene Expression Profile by Limiting Diffusion

Abstract

We seek to elucidate the role of macromolecular crowding in transcription and translation. It is well known that stochasticity in gene expression can lead to differential gene expression and heterogeneity in a cell population. Recent experimental observations by Tan et al. have improved our understanding of the functional role of macromolecular crowding. It can be inferred from their observations that macromolecular crowding can lead to robustness in gene expression, resulting in a more homogeneous cell population. We introduce a spatial stochastic model to provide insight into this process. Our results show that macromolecular crowding reduces noise (as measured by the kurtosis of the mRNA distribution) in a cell population by limiting the diffusion of transcription factors (i.e. removing the unstable intermediate states), and that crowding by large molecules reduces noise more efficiently than crowding by small molecules. Finally, our simulation results provide evidence that the local variation in chromatin density as well as the total volume exclusion of the chromatin in the nucleus can induce a homogenous cell population.

The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation

“…In 32 we illustrated that macromolecular crowding can control gene expression fluctuations. Here we present a model based on the macromolecular crowding effects of chromatin structure to reveal the underlying principles of population heterogeneity and its regulation.…”

WITHDRAWN: Steric blockage of lysenin toxin by crowding

“…Nowadays, macromolecular crowding has been identified as a biologically significant factor both in cytoplasm and membrane. There is clear evidence of the role of crowding in the regulation on the gene expression 3 , on the gating energies of membrane proteins 4 , and on the membrane protein conformational landscape 5,6 . As factors incorporated to the already crowded membranes, Pore Forming Toxins (PFTs) 7 are emerging as important elements to reproduce crowding conditions in vitro, allowing to study crowding effects 8,9,10 .…”

Physicochemical Properties of Chromosomes in Live Cells Characterized by Label-Free Imaging and Fluorescence Correlation Spectroscopy

“…Interestingly, the D value in DM cell cultured by hypertonic media showed much smaller than the theoretical value. Since hypertonic stress enforces molecular crowding in the cellular components due to the osmotic extraction of water from the cells (Richter et al, 2007), these results suggest that molecular diffusion in the cytosol and chromosome at high osmolality is largely affected by molecular crowding induced by the hypertonic conditions (Golkaram et al, 2016;Park et al, 2015).…”