A MATHEMATICAL MODEL FOR THE GROWTH OF A SINGLE BACTERIAL CELL *

Changes in bacterial cell size and shape due to changes in the abiotic environment have been observed for decades.’ The changing surface-to-volume ratio has the potential of profoundly affecting cell Yet very few of the multitude of mathematical models suggested for the description of bacterial growth6’ allow for the possible inclusion of the effects of changes in cell geometry; most are models of how a whole culture will grow. The purpose of this paper is to describe a mathematical model for the growth of an individual cell. Other advantages of an individual cell model are the ease with which temporal and spatial events in the cell division cycle can be included. It is impossible to include such information in nonsegregated mathematical models and often computationally difficult to include such events in segregated models. Cell structure and the interactions of major metabolic pathways can readily and accurately be included in a single-cell model. Although similar information can be incorporated in whole culture models, such efforts have often been marred by subtle errors in model formulation’ which would have been readily avoided in formulating an individual cell model. Single-cell models do have limitations. They are accurate representations of the growth of a bacterial culture only if the moments of distribution of cellular properties higher than the first-order are not important. The single-cell model should accurately represent the growth of a synchronous culture and perhaps growth in a steady-state continuous culture. However, such an assumption would obviously fail in a culture where only 50% of the cells were viable. Such a limitation could conceivably be removed by dividing the culture into different subpopulations based on, for example, cell size and composition, and assigning one or more individual cells to that fraction. Several models for the growth of an individual cell have been po~tulated.~*~-” These models all contain one or more arbitrary constraints on the computer “growth” of the cell. Examples of such constraints are mode of growth (exponential), timing of cell division, culture conditions (balanced growth only), no explicit accounting of the abiotic environment (e.g. nutrient uptake), and cell shape. In this paper we present for the first time a single-cell model unconstrained in any way by the investigator. All that needs to be specified is the initial nutrient composition in the medium and temperature and pH. Cell growth, DNA initiation, crosswall formation, changes in cell size and

[1]  C. Helmstetter,et al.  Cell Division During Inhibition of Deoxyribonucleic Acid Synthesis in Escherichia coli , 1968, Journal of bacteriology.

[2]  H. M. Tsuchiya,et al.  Studies in intermicrobial symbiosis. Saccharomyces cerevisiae and Lactobacillus casei. , 1972, Canadian journal of microbiology.

[3]  S. Cooper,et al.  Chromosome replication and the division cycle of Escherichia coli B/r. , 1968, Journal of molecular biology.

[4]  A G Fredrickson,et al.  Formulation of structured growth models. , 2000, Biotechnology and bioengineering.

[5]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[6]  W. Hempfling,et al.  Effects of varying the carbon source limiting growth on yield and maintenance characteristics of Escherichia coli in continuous culture , 1975, Journal of bacteriology.

[7]  U. Schwarz,et al.  Regulation of polar cap formation in the life cycle of Escherichia coli. , 1972, Journal of supramolecular structure.

[8]  M A Savageau,et al.  Glutamate dehydrogenase from Escherichia coli: purification and properties , 1975, Journal of bacteriology.

[9]  B. Thorell,et al.  Changes in Glycogen and Nitrogen-containing Compounds in Escherichia coli B during Growth in Deficient Media. I. Nitrogen and Carbon Starvation. , 1956 .

[10]  G. Stent,et al.  Nucleoside triphosphate pools and the regulation of RNA synthesis in E. coli. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Daniel D. McCracken,et al.  Numerical methods and FORTRAN programming , 1964 .

[12]  C. Woldringh,et al.  Elongation of rod-shaped bacteria. , 1977, Journal of theoretical biology.

[13]  P. Dennis,et al.  Macromolecular Composition During Steady-State Growth of Escherichia coli B/r , 1974, Journal of bacteriology.

[14]  S. J. Pirt,et al.  Principles of microbe and cell cultivation , 1975 .

[15]  I. C. Gunsalus,et al.  CHAPTER 1 – Energy-Yielding Metabolism in Bacteria , 1961 .

[16]  J. Mandelstam,et al.  Turnover of protein and nucleic acid in soluble and ribosome fractions of non-growing Escherichia coli. , 1960, Biochimica et biophysica acta.

[17]  H. Winkler,et al.  The role of energy coupling in the transport of beta-galactosides by Escherichia coli. , 1966, The Journal of biological chemistry.

[18]  T. Kornberg,et al.  Deoxyribonucleic acid synthesis in cell-free extracts. IV. Purification and catalytic properties of deoxyribonucleic acid polymerase III. , 1972, The Journal of biological chemistry.

[19]  B P Zeigler,et al.  System theoretic analysis of models: computer simulation of a living cell. , 1970, Journal of theoretical biology.

[20]  F. G. Bader,et al.  Analysis of double‐substrate limited growth , 1978, Biotechnology and bioengineering.

[21]  H. M. Tsuchiya,et al.  Comments on microbial growth rate , 1975 .

[22]  U. Schwarz,et al.  Autolytic enzymes and cell division of Escherichia coli. , 1969, Journal of molecular biology.

[23]  F. Young Biochemistry , 1955, The Indian Medical Gazette.

[24]  D. Clark,et al.  Nucleoside Triphosphate Pools in Synchronous Cultures of Escherichia coli , 1971, Journal of bacteriology.

[25]  P. Painter,et al.  Mathematics of microbial populations. , 1968, Annual review of microbiology.

[26]  H. M. Tsuchiya,et al.  Mathematical Models for Fermentation Processes , 1970 .

[27]  M. Shuler,et al.  Predictions of cellular growth patterns by a feedback model. , 1977, Journal of theoretical biology.

[28]  H. Bremer,et al.  Establishment of exponential growth after a nutritional shift-up in Escherichia coli B/r: accumulation of deoxyribonucleic acid, ribonucleic acid, and protein , 1977, Journal of bacteriology.

[29]  A. Henrici Morphologic Variation and the Rate of Growth of Bacteria , 1928 .

[30]  A. G. Marr,et al.  Growth and division of Escherichia coli , 1966, Journal of bacteriology.

[31]  E. Previc Biochemical determination of bacterial morphology and the geometry of cell division. , 1970, Journal of theoretical biology.

[32]  C. G. Sinclair,et al.  Models for the continuous culture of microorganisms under both oxygen and carbon limiting conditions , 1975 .

[33]  J. Hoffman The cellular functions of membrane transport , 1963 .

[34]  J. Heinze,et al.  The effects of organic solvents on Escherichia coli DNA polymerase III. , 1975, Biochimica et biophysica acta.

[35]  C. Helmstetter,et al.  Initiation of chromosome replication in Escherichia coli. II. Analysis of the control mechanism. , 1974, Journal of molecular biology.

[36]  F. Neidhardt EFFECTS OF ENVIRONMENT ON THE COMPOSITION OF BACTERIAL CELLS. , 1963, Annual review of microbiology.

[37]  D J Park,et al.  The hierarchical structure of metabolic networks and the construction of efficient metabolic simulators. , 1974, Journal of theoretical biology.

[38]  G. Westöö,et al.  Continuous Culture Studies on Glycogen Synthesis in Escherichia coli B. , 1957 .

[39]  M. Schaechter,et al.  Control of cell division in bacteria. , 1974, Bacteriological reviews.

[40]  C. Helmstetter,et al.  DNA synthesis during the division cycle of three substrains of Escherichia coli B/r. , 1976, Journal of molecular biology.

[41]  N. Sharon The bacterial cell wall. , 1969, Scientific American.

[42]  J. Ezzell,et al.  Altered hexose transport and salt sensitivity in cyclic adenosine 3',5'-monophosphate-deficient Escherichia coli , 1975, Journal of bacteriology.

[43]  F. Heinmets,et al.  Analysis of Normal and Abnormal Cell Growth , 1966, Springer US.

[44]  C. Boylen,et al.  Intracellular Substrates for Endogenous Metabolism During Long-Term Starvation of Rod and Spherical Cells of Arthrobacter crystallopoietes , 1970, Journal of bacteriology.

[45]  N Nanninga,et al.  Size variations and correlation of different cell cycle events in slow-growing Escherichia coli , 1978, Journal of bacteriology.

[46]  R. H. Pritchard Review lecture on the growth and form of a bacterial cell. , 1974, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[47]  H. M. Tsuchiya,et al.  Dynamics of Microbial Cell Populations , 1966 .

[48]  Bernard P. Zeigler,et al.  Computer Simulation of a Living Cell: Metabolic Control System Experiments , 1971 .

[49]  Kaback Hr The Role of the Phosphoenolpyruvate-phosphotransferase System in the Transport of Sugars by Isolated Membrane Preparations of Escherichia coli , 1968 .

[50]  Automated instrument for measuring biological transport kinetics over intervals of a few seconds , 1974, Biotechnology and bioengineering.

[51]  R. K. Finn,et al.  Equations of substrate‐limited growth: The case for blackman kinetics , 1973, Biotechnology and bioengineering.

[52]  E. Davison Simulation of cell behavior: normal and abnormal growth. , 1975, Bulletin of mathematical biology.