Biology Reference
In-Depth Information
fibrils. Again, there seems to be a critical transition in this process, the rate of growth up to the
size of about five trimers being modest but much faster thereafter.
18
This may help to ensure
that collagen polymerization tends to make a few large fibrils rather than many tiny ones. The
staggered binding seen in the dimer and trimer is also seen in the fibrils. The stagger creates
zones of the fibril that include 'gaps' capable of trapping electron-microscopic stains such as
phosphotungstate, and regions with no gaps that stain only lightly. The overall appearance of
a fibril stained in this way is therefore one of alternating light and dark bands, the periodicity
of which is a little under 70 nm.
When samples of a collagen solution are taken throughout fibril self-assembly, it seems
that maximum fibril diameter is reached when the fibril has only reached about 20 percent
of its final size, suggesting that subsequent addition of collagen is at the fibril's ends. The
reason for this is not yet clear, but it suggests a subtle property of the self-assembling system
that is sensitive to the diameter of the complete fibre. The ends of growing fibrils tend to be
tapered, and it is possible that the structure of these ends guides the arrival of new compon-
ents into the correct 'stagger'. In most cases
in vitro
and
in vivo
, collagen proteins self-
assemble in a staggered side-by-side arrangement in which all chains lie in the same direction
in terms of their NH
2
/
COOH polarity. Such fibrils are described as unipolar (bipolar fibrils
can occur in some
in vitro
systems
19
and probably
in vivo
too,
20
but they will not be discussed
further here).
It is important to note that the fibril diameters of collagens assembled
in vitro
from puri-
fied collagens isolated from tissues generally differ from their native diameters in those
tissues. Therefore, while collagen fibrils clearly self-assemble, in living systems this self-
assembly must be subject to additional regulation. This is a general pattern; self-assembly
of components is a vital part of most morphogenetic processes, but it is regulated to
a greater or lesser extent by other factors and, when the extent of regulation is particularly
great
d
especially when feedback is involved
d
the term 'self-assembly' ceases to be used at
all and other terms such as 'self-organization' come to be used instead. It is also important
to note that the assembly of fibrils goes only part of the way to assembling biologically
useful collagen structures: in real extracellular matrices, collagens associate with a large
number of other matrix components and with cellular receptors. Together, these organize
them into an appropriate spatial arrangement
d
for example a precise, optically transparent
orthogonal array of fine fibrils in the cornea of the eye or a dense, parallel array of thick
fibrils in the Achilles tendon. These arrangements certainly do not arise by simple self-
assembly of their components, and are subject to very fine spatial regulation by the cells
that lay them down.
THRE
E-DIMENSIONAL SELF-ASSEMBLY: SIMPLE VIR
USES
The only complete organisms capable of building themselves entirely by simple self-
assembly are small viruses. A striking example is provided by tobacco mosaic virus
(TMV). The genome of this virus consists of a single-stranded RNA molecule of 6395
nucleotides that has an inverted 7-methyl-G cap at the 5
0
end.
21,22
In the mature virus
particle, this RNA is packaged in 2131 molecules of coat protein, each protein unit
making contact with three nucleotides of the RNA. The wedge-shaped protein units
