Biomedical Engineering Reference
In-Depth Information
be the explanation for the improvement. While culturing, it is important to provide
extracellular signals appropriate for the cell in order to achieve an optimal function
or proliferative response. ECM molecules also interact with soluble factors, alter-
ing their bioactivity and transmitting signals across the cell membrane to cytoplas-
mic molecules that, in turn, initiate cascades of events involving cytoskeleton and
nucleus. These “nuclear events” affect specific gene expression that reciprocally
regulates ECM structures and contents.
7.2.2 Cell-SolubleFactorInteractions
Soluble factors play an important role in various functions including cell growth
and the secretion of other soluble factors. In general, soluble factors are proteins,
show very high specificity in interactions, are members of a family of related pro-
teins, and are pleiotropic (i.e., are able to mediate a variety of actions on different
cells).
Autocrine signaling
is a way that cells self-regulate their extracellular envi-
ronment by secreting soluble factors, which in turn affects the way that the cell
functions. Some cells regulate their growth by this signaling.
Paracrine signaling
occurs when soluble factors released by cells are taken up by neighboring cells.
Paracrine signals are short-lived with local effects and play an important role in
early development.
Hormonal signaling
occurs due to the released signaling mol-
ecule from the endocrine glands being collected and distributed via bloodstream.
Synaptic signaling
occurs through the nervous system via neurons producing neu-
rotransmitters close to the target cells. Synaptic signals persist briefly. The serum
provides a good source of soluble factors, of which only a few are known such as
vitamins and hormones. As a serum is formed, the platelets in the whole blood
release their soluble factors, many of which are called the
wound healing growth
factors
. With the advent of gene cloning and recombinant DNA technology, many
of the genes encoding growth factors have been identified, and these genes are used
to produce large amounts of highly purified growth factors that are added to the
cell culture medium. Some soluble factors that play an important role in influencing
the immune system are referred to as cytokines.
Soluble factors typically transduce the signal into the nucleus by binding to
other proteins, for which the name
receptors
is in common use. During these inter-
actions, soluble factors are referred to as
ligands
. Small hormones such as steroid
hormones readily diffuse across the plasma membrane and bind with cytosolic
receptors or directly enter the nucleus and then bind to intranuclear receptors.
These activated receptors act like transcription factors, leading to the production
of mRNA and the protein synthesis or an increased rate of secretion of specific
molecules. These types of soluble factors are called
first messengers
because they
do not depend on other molecular interactions that may be required to achieve the
end results. However, many soluble factors do not readily diffuse across the plasma
membrane. They exert their influence on intracellular processes by interaction with
cell surface receptors [Figure 7.2(b)]. In these cases, binding activates the receptors,
which initiate a sequence of biochemical reactions inside the cell to produce other
messengers that will transfer the signal to alter necessary function. These are called
second messengers,
which include cyclic adenosine mono phosphate (cAMP), cyclic
guanosine monophosphate (cGMP), diacylglycerol (DAG), inositol triphosphate
