(A short talk to be presented at the 108th Statistical Mechanics Conference, Hill Center for
Mathematical Sciences, Rutgers University, Piscataway, N.J., December 16-18, 2012.
The Metabolic Tetractys: The Four Forces that Determine the Whole-Cell RNA Kinetic
Patterns (or RNA Dissipatons).
Sungchul Ji, Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy,
Piscataway, N.J. 08854.
The cell force can be operationally defined as any physical agent or entity that can cause changes
in cell metabolism. For example, switching the nutrient from glucose to galactose [1] or shifting
the environmental temperature from 25° to 37° [2] in cell suspensions of budding yeast
constitute cell forces since they cause rapid changes in the intracellular levels of millions of
RNA molecules in individual cells, each RNA molecule being encoded by one of the 6,300
genes in the yeast genome. When these forces are applied to yeast cells, the intracellular RNA
levels exhibit two kinds of changes as revealed by the microarray technique – the RNA-specific
and RNA-non-specific kinetic patterns [3]. The former patterns account for about 15% and the
latter 85 % of the whole intracellular RNA population. These patterns of changes in the
intracellular RNA levels can be viewed as examples of the dissipative structures of Prigogine
(1917-2003), or RNA dissipatons more briefly, since they disappear when energy supply to cells
is blocked [1, 3]. It is interesting to note that RNA dissipatons in the chemical concentration
space are analogous to the Newtonian trajectories of moving bodies in the geometric space.
Hence, just as the Newtonian force alters the trajectories of moving objects, so the cell force is
postulated to cause changes in the RNA trajectories (or RNA dissipatons) in the chemical
concentration space. Unlike the Newtonian forces which are external to moving or resting
objects, the forces acting on RNA dissipatons in living cells can be divided into the external and
the internal forces (as explained in Table 1) and only the latter can be identified with the cell
force that was first invoked in 1991 in analogy to the strong force in physics [4].
Table 1. The tetractys of the forces that determine the RNA dissipatons in living cells.
Metabolic Forces, or the forces that cause changes in metabolic rates
Internal
Specific
Non-Specific
RNA- specific cell force [3]
ATP-mediated cell force [3]
External Glucose replacement with
galactose [1]
Glucose replacement with
galactose [1]
*The forces that cause changes in metabolic rates.
References:
[1] Garcia-Martinez, J., Aranda, A. and Perez-Ortin, J. E. (2004). Genomic Run-On Evaluates
Transcription Rates for all Yeast Genes and Identifies Gene Regulatory Mechanisms, Mol Cell
15, 303-313.
[2] Castells-Roca L, García-Martínez J, Moreno J, Herrero E, Bellí G, et al. (2011). Heat
Shock Response in Yeast Involves Changes in Both Transcription Rates and mRNA Stabilities.
PLoS ONE 6(2): e17272. doi:10.1371/journal.pone.0017272
[3] Ji, S., Chaovalitwongse, A., Fefferman, N., Yoo, W. & Perez-Ortin, J. E. (2009a).
Mechanism-based Clustering of Genome-wide mRNA Levels: Roles of Transcription and
Transcript-Degradation Rates, in Clustering Challenges in Biological Networks, S. Butenko, A.
Chaovalitwongse, and P. Pardalos, (eds.), World Scientific Publishing Co., Singapore, pp. 237255. Available at conformon.net under Publications > Proceedings and Abstracts.
[4] Ji, S. (2012). The Cell Force: Microarray Evidence. In: Molecular Theory of the Living
Cell: Concepts, Molecular Mechanisms, and Biomedical Applications. Springer, New York.
Section 12.13, pp. 444-448.