Biomedical Engineering Reference
In-Depth Information
where (1
−
f
) is the fraction of cell that is not dividing. Nevertheless,
μ
depends on
the quantity of the substrate. Hence, relating
to the substrate concentration is nec-
essary. For proliferation limited by one substrate,
S
, a widely used Monod equation
(named afer French biologist Jacques Monod) is
μ
S
KS
μ
μ =
max
+
s
μ
max
is the maximum specific growth rate constant [hr
−1
] and
K
s
is the
Monod constant. This empirically derived equation for bacterial cultures is similar
to the Michaelis-Menten model. The Monod equation does not consider the fact
that cells may nee d a substrate (or may synthesize the product) even when
they
do not proliferate. Hence, more sophisticated proliferation models are developed
combining receptor-ligand interactions.
where
7.3.2.2 Consideration of Cell Death
Cell death is part of the normal development and maturation cycle and is the com-
ponent of many responses of cells to pathogens and to endogenous modulations,
such as inflammation and disturbed blood supply. In the treatment of cancer, the
major approach is the removal of the cancerous tissue and/or the induction of cell
death in cancerous cells by radiation, toxic chemicals, and antibodies and/or cells
of the immune system. On the other hand, cell death decreases the overall biophar-
maceutical yield in large-scale cell cultures. To optimize cell viabilities and protein
yields in culture, one has to develop strategies for controlling cell death. Cell death
occurs in two general forms: necrosis and apoptosis. Necrosis results from imme-
diate, extreme conditions that physically damage cells causing them to swell and
rupture, releasing their cellular contents into the surrounding environment. Necro-
sis occurs without the consumption of energy, without DNA cleavage, and without
the role of mitochondria. It is not regulated by any intracellular signaling pathway
and varies from cell type to cell type. Necrosis can be controlled by optimizing en-
vironmental conditions in large scale cell cultures. Apoptosis (also referred to as a
type of programmed cell death) is a regulated physiological process resulting from
a nonlethal stimulus that activates a cellular cascade of events culminating in cell
death leading to the removal of unnecessary, aged, or damaged cells. Apoptosis is
important for removing viral-infected cells, cancer cells, cytotoxic T-cells to pre-
vent self-attack, and cells with DNA abnormality. Apoptosis allows the formation
of vital organs by removing excessive cells in the area, sloughing off inner lining
of the uterus at the start of menstruation, and the formation of synapses between
neurons in the nervous system. Apoptosis is energetically dependent and geneti-
cally regulated by the interplay of pro- and anti-apoptotic proteins. Although the
apoptotic program is complex and the cellular events involve the activation of many
signaling cascades, apoptosis is characterized by cell shrinkage, plasma membrane
blebbing, and DNA fragmentation. Blebbing involves the shedding of membrane
fragments from the cell in the form of apoptotic bodies that often include cytosolic
and nuclear contents.
