Structured kinetic model:

Compartmental models
In the simplest structured models, the biomass is
compartmentalized into a small number of components.
Sometimes these components have an approximate
biochemical definition, as in a synthetic component (RNA and
precursors) and a structured component (DNA and
component). Alternatively, the compartments may be defined
as an assimilatory component and a synthetic component.
Another interpretation which has been used to guide
formulation of simple compartmental models is that of a
bottleneck in metabolism.
Structured models containing a small number of
variables may also be justified on the basis of some concepts
from systems dynamics. Each class of reaction and transport
events which occurs in a cell population-molecular collisions,
chemical reactions, diffusions, turnover of RNA, protein
synthesis, increase in cell number, completion of batch
process, spontaneous mutation-has characteristic relaxation
time, or time to reach steady state after a perturbation. These
relaxation times ranges from fractions of second to hours.
What is important in modeling, from a systems dynamics
viewpoint, is the relaxation time between the time scale of
changes in cells environment and the spectrum of relaxation
times of cellular processes. Those cellular processes that
respond very fast to environmental changes may be assumed
to be in quasi-steady state. For the other extreme, where the
relaxation time for some cellular process is very large
compared to ,that class of cellular processes may be
assumed to be ``frozen at the initial state. For example,

significant genetic changes are not usually expected during a

single batch cultivation.
It has been found for many complicated systems that
there are typically only two or three system relaxation times in
the same range as the time scale for environmental changes,
justifying approximating the dynamics of a large system using
a low order model with only two or three system variables.
However, it is often difficult or impossible to relate some of
these variables to measurable, physical quantities
characteristic of the system. We consider next some examples
of simple, compartmental structured kinetic models of cell
population growth.
Williams[16]proposed a two-compartment model which
reproduces several aspects of batch growth dynamics
surprisingly well. The major postulates of this modeling are
following:
1. The synthetic (1) portion is produced by uptake of external
nutrient S with (component 1 mass/substrate mass) yield of
coefficient Y. The rate of cell synthetic component formation is
first order in total density x (cell mass/culture volume) and
nutrient mass concentrations (substrate mass/culture volume).
2. The structural-genetic (2) cell component is produced from
component 1 at a rate proportional to
3. Doubling time of component 2 is necessary and sufficient
for cell division. Accordingly, the cell number density is
proportional to the density of component 2 in the culture.
4. Biomass is comprised solely of components 1 & 2.
Restarted in equation form for a well-mixed batch reactor, the
model is

The model has been used to stimulate batch growth

using a stationary, nutrient-exhausted inoculum, which
corresponds to =0. The results, mimic several frequently
observed features of batch microbial cultures including
1.Existance of a lag phase in which cell increases.
2.An exponential-growth phase where cell size is maximum
3.A change in composition of cells during the cycle. Since
these changes are evident even during the exponential
phase, apparently growth is never exactly balanced.
4.A stationary phase with relatively small cells.
Notice in particular that the changes with time in cell mass
density and in cell number density are not parallel nor
proportional; that is, single-cell mass is not constant but
depends on growth rate and even on growth-rate history.
Detailed studies of microbial population growth is based on
the E. coli and S.cerevisiae cell cycles shown similar results.
Based on these cases, it appears that the dynamics of cell
mass changes may often be accurately approximated by
relatively simple models, while calculating the dynamics of
cell numbers is much more complicated.
Some elaborations on the above model are summarized
in the sketches. In the two-compartment model of Harder and
Roels [17], the G component corresponds to enzymes which
catalyze conversion of substrate to biopolymer building
blocks, and the balance of the cells constituents are in
component K which is formed from nutrient S at a rate which
depends on the quantity of G. Interconversion of G and K by
polymerization and depolymerization reactions introduces
maintenance metabolism into this simple two-component cell.

The three-component cell has constituents with more welldefined biochemical identity: K denotes RNA, G protein and R
the remaining biomass. Turnover of the K and G
compartments adds features of maintenance to the model.
Compared with some of the more elaborate structured
models are examined below, these small compartmental
models are relatively uncomplicated mathematically and
contain relatively few kinetic parameters. These models have
been used with some success in describing different
unbalanced growth situations. On the other hand, the absence
in some cases of a clear biochemical definition of the
compartment components make model validation and
parameter estimation more difficult. With such models, we
cannot make use of known features of the cells metabolic
pathways, molecular controls and cell cycle operation. To use
this knowledge in kinetic modeling, cell representations with
more structure that is, more components and intracellular
reactions and interactions are required.