scholarly journals Cell growth rate dictates the onset of glass to fluid-like transition and long time super-diffusion in an evolving cell colony

2017 ◽  
Author(s):  
Abdul N Malmi-Kakkada ◽  
Xin Li ◽  
Himadri S. Samanta ◽  
Sumit Sinha ◽  
D. Thirumalai

Collective migration dominates many phenomena, from cell movement in living systems to abiotic self-propelling particles. Focusing on the early stages of tumor evolution, we enunciate the principles involved in cell dynamics and highlight their implications in understanding similar behavior in seemingly unrelated soft glassy materials and possibly chemokine-induced migration of CD8+T cells. We performed simulations of tumor invasion using a minimal three dimensional model, accounting for cell elasticity and adhesive cell-cell interactions as well as cell birth and death to establish that cell growth rate-dependent tumor expansion results in the emergence of distinct topological niches. Cells at the periphery move with higher velocity perpendicular to the tumor boundary, while motion of interior cells is slower and isotropic. The mean square displacement, Δ(t), of cells exhibits glassy behavior at times comparable to the cell cycle time, while exhibiting super-diffusive behavior, Δ(t) ≈tα(α> 1), at longer times. We derive the value ofα≈ 1.33 using a field theoretic approach based on stochastic quantization. In the process we establish the universality of super-diffusion in a class of seemingly unrelated non-equilibrium systems. Super diffusion at long times arises only if there is an imbalance between cell birth and death rates. Our findings for the collective migration, which also suggests that tumor evolution occurs in a polarized manner, are in quantitative agreement within vitroexperiments. Although set in the context of tumor invasion the findings should also hold in describing collective motion in growing cells and in active systems where creation and annihilation of particles play a role.

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 109-109
Author(s):  
Matthew S Crouse ◽  
Wellison Jarles Da Silva Diniz ◽  
Joel Caton ◽  
Carl R Dahlen ◽  
Lawrence P Reynolds ◽  
...  

Abstract We hypothesized that supplementation of one-carbon metabolites (OCM: methionine, folate, choline, and vitamin B12) to bovine embryonic tracheal fibroblasts in divergent glucose media would alter cytosine methylation, and alterations in cytosine methylation will reflect biological processes matching previously improved mitochondrial respiration, cell proliferation, and cell growth rate data. Cells were cultured with 1g/L glucose (Low) or 4.5g/L glucose (High). Control medium (CON) contained basal concentrations of folate (0.001g/L), choline (0.001g/L), vitamin B12 (4µg/L), and methionine (0.015g/L). The OCM were supplemented at 2.5 and 5 times (2.5X and 5X, respectively) the CON media, except methionine was limited to 2X across all supplemented treatments. Cells were passaged three times in their treatment media before DNA extraction. Reduced representation bisulfite sequencing was adopted to analyze and compare the genomic methylation patterns within and across treatments using edgeR. Biological processes (BP) were retrieved based on the nearest genes of differentially methylated cytosines (P < 0.01) for each comparison between treatments. In both Low and High treatments, greater OCM increased the proportion of hypomethylated vs. hypermethylated cytosines. Functional analyses pointed out positive regulation of BP related to energy metabolism, except for the contrasts within the High group. Among the BP, we can highlight positive regulation of: GTPase activity, catalytic activity, molecular function, protein modification processes, phosphorylation, protein phosphorylation, cellular protein metabolic processes, MAPK cascade, and metabolic processes. These data support previously reported results from this experiment that showed increased mitochondrial respiration, cell proliferation, and growth rates with increasing OCM levels. We interpret these data to imply that when energy and OCM requirements are met for growth and basal methylation levels, DNA methylation levels decrease which may allow for greater transcription. Thus, OCM can be utilized for other functions such as polyamine synthesis, nucleotide synthesis, energetic metabolites, and phosphatidylcholine synthesis. USDA is an equal opportunity provider and employer.


1993 ◽  
Vol 6 (1) ◽  
pp. 27
Author(s):  
Sai C. Chan ◽  
Shi-Hua Li ◽  
William R. Henderson ◽  
Jon M. Hanifin

1973 ◽  
Vol 59 (2) ◽  
pp. 471-479 ◽  
Author(s):  
Brian Storrie

In an attempt to understand further the mechanism of the morphological and functional "reverse transformation" of CHO-K1 cells induced by dibutyryl adenosine cyclic 3',5'-monophosphate (cAMP) and testosterone, the kinetics of variation in the susceptibility of cells to rounding after the addition or deletion of dibutyryl cAMP and testosterone have been investigated. Changes in susceptibility to cell rounding upon removal of divalent cations or pulse exposure to concanavalin A were complete within 0.5–1 h after addition or deletion of drug. In comparison, the gross conversion of CHO-K1 cells from epithelial- to fibroblast-like morphology after drug treatment or the converse change after drug removal required 8 or 4 h, respectively. The effects on cell rounding are not caused by an effect of dibutyryl cAMP upon cell growth rate. Inhibitor experiments indicate that the changes investigated do not require continued RNA or protein synthesis and are not prevented by agents which depolymerize microtubules.


2021 ◽  
Author(s):  
Yufei Wu ◽  
Paul Janmey ◽  
Sean X. Sun

In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influences the cell growth rate as well as the cytoplasm/nucleoplasm ratio. Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cytoplasm/nucleoplasm ratio, the cell must optimally control groups of kinetic parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, using an extension of our model and single cell RNAseq data, it is possible to construct a detailed proteome distribution, provided that a cell division mechanism is known.


1985 ◽  
Vol 5 (5) ◽  
pp. 1051-1057
Author(s):  
M Santos ◽  
J S Butel

Cell growth control appears to be drastically altered as a consequence of transformation. Because the cell surface appears to have a role in modulating cell growth and simian virus 40 (SV40)-transformed cells express large T antigen (T-Ag) in the plasma membrane, we investigated whether surface T-Ag expression varies according to cell growth rate. Different growth states were obtained by various combinations of seeding density, serum concentration, and temperature, and cell cycle distributions were determined by flow microcytofluorometry. Actively dividing SV40-transformed mouse cell cultures were consistently found to express higher levels of surface T-Ag and T-Ag/p53 complex than cultures in which cells were mostly resting. In addition, the T-Ag/p53 complex disappeared from the surface of tsA7-transformed cells cultured under restrictive conditions known to induce complete growth arrest (39.5 degrees C), although the surface complex did not disappear from other tsA transformants able to keep cycling at 39.5 degrees C. These results suggest that surface SV40 T-Ag or surface T-Ag/p53 complex, or both, are involved in determining the growth characteristics of SV40-transformed cells.


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