Biomedical Engineering Reference
In-Depth Information
Model Functioning
cellular gene produces a protein, the concentration
of the protein is checked to be below the value of
the lower communication threshold. If such is the
case, the protein is kept inside the cell cytoplasm.
If the concentration is higher than the lower com-
munication threshold value but lower than the up-
per communication threshold, the cell sends that
protein to one of its randomly selected neighbour
proteins. If the concentration exceeds the higher
communication threshold, the protein is sent to
all the neighbour cells. The third implemented
threshold is the apoptosis threshold; it determines
the protein concentration that is needed to induce
cellular death. Finally, the mitosis and apoptosis
procedures are executed when the cell generates
certain types of proteins that were identified as
“special”. Therefore, if a protein whose sequence
was identified as leftwards mitosis is produced and
the cell has not been divided during that “cellular
cycle”, the action will be executed. Five special
proteins were identified in the system: apoptosis,
upwards mitosis, downwards mitosis, leftwards
mitosis, and rightwards mitosis.
The different events of a tissue are managed in
the cellular model by means of “cellular cycles”.
Such “cycles” will contain all the actions that can
be carried out by the cells, restricting sometimes
their occurrence. The “cellular cycles” can be
described as follows:
The functioning of genes is determined by their
type, which can be constituent or regulating. The
transcription of the encoded protein occurs when
the promoters of the non-constituent genes appear
in a certain rate at the cellular cytoplasm. On the
other hand, the constituent genes are expressed
during all the “cycles” until such expression is
inhibited by the present rate of the promoter
genes.
Protein Concentration Percent
>=
(Distance
+
1) * Activation Percent
(1)
The activation of the regulating genes or the
inhibition of the constituent genes is achieved if
the condition expressed by equation (1) is fulfilled,
where
Protein Concentration Percentage
repre-
sents the cytoplasm concentration of the protein
that is being considered;
Distance
stands for the
Hamming distance between one promoter and the
considered protein; and
Activation Percentage
is the minimal percentage needed for the gene
activation that is encoded in the gene. This equa-
tion is tested on each promoter and each protein.
If the condition is fulfilled for all the promoters,
that gene is transcribed. According to this, if
gene-like promoters exist in a concentration
higher than the encoded concentration, they can
also induce its transcription, similarly to what
happens in biology and therefore providing the
model with higher flexibility. If the condition is
fulfilled for each promoter, the gene is activated
and therefore transcribed.
After the activation of one of the genes, three
things can happen: the generated protein may be
stored in the cell cytoplasm, it may be commu-
nicated to the neighbour cells, or it may induce
cellular division (mitosis) and/or death (apoptosis).
In order to modulate these behaviours, we defined
three threshold values in the cellular system, two
of which manage the communications, whereas
the third regulates the system apoptosis. When a
•
Actualisation of the life time of proteins in
the cytoplasm
•
Verification of the life status of the cell (cel-
lular death)
•
Calculation of the genes that react and
perform the special behaviour that may be
associated to them
•
Communication between proteins
During the first stage, the functioning of each
cell checks the existence of proteins in the cyto-
plasm that may affect the promoters of the dif-
ferent DNA genes. This information is then used
to determine which are genes will be transcribed
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