Tissue Engineering - Introduction to Biomedical Engineering - page 313

These means of cellular communication differ in terms of their characteristic time and
length scales, as well as in their specificity. Consequently, each is most suitable to convey
a particular type of a message.

Soluble Growth Factors
Growth factors are small proteins that are on the order of 15,000 to 20,000 Dalton in size
(one Dalton is the weight of the hydrogen atom and is a typical unit used to describe the
size of molecules). They are relatively chemically stable and have long half-lives unless they
are specifically degraded. Initially, growth factors were discovered as active factors that
originated in biological fluids. For instance, erythropoetin was first isolated from urine and
the colony stimulating factors from conditioned medium from particular cell lines. The pro-
tein could be subsequently purified and characterized. With the advent of DNA technology,
growth factors can now be cloned directly as ligands for known receptors. This procedure
was used to isolate thrombopoietin, as the c-kit

ligand. Growth factors are produced by a signaling cell and secreted to reach a target cell.

c-mpl ligand and the stem cell factor as the

EXAMPLE PROBLEM 6.2
What is the maximal secretion rate of protein?

Solution
The maximal secretion rate of a protein from a single gene in a cell can be estimated based on
the maximal rates of transcription and translation. Such estimates have been carried out for the
production of immunoglobulins (MW 150,000 D), whose genes are under the control of strong

promoters. The estimate shows that the maximal secretion rate is on the order of 2,000 to 8,000
protein molecules per cell per second, which corresponds to about 1 pg per cell per hour. This
estimate compares favorably with measured maximal secretion rates. Since growth factors tend
to be about one-tenth the size of immunoglobulin, a correspondingly higher secretion rate in
terms of molecules per cell per time would be expected, although the total mass would stay the
same. The secretion rates of protein from cells are expected to be some fraction of this maximum
rate, since the cell is making a large number of proteins at any given time.

¼

Growth factors bind to their receptors, which are found in cellular membranes, with high
affinities. Their binding constants are as low as 10 to 100 pM. The binding of a growth factor
to a receptor is described as

½ G ½ R
½ G : R ¼ K a

G þ R , G : R

, and ð 6 : 11 Þ

where [G], [R], and [G:R] are the concentrations of the growth factor receptor and the
bound complex, respectively, and K a is the binding constant. Since the total number of
receptors (R tot ) in the system is constant, we have the mass conservation quantity:
R tot ¼½ R þ½ G : R ð 6 : 12 Þ