Biology Reference
In-Depth Information
in the microtubule). If, however, hydrolysis of GTP takes place on a tubulin monomer while it
is still in a terminal position, its binding to the microtubule becomes unstable and it falls away.
Statistically, it is likely that, by the time a still-terminal tubulin has lost its GTP, the tubulin
units behind it, which have been present in the microtubule for longer, will also have hydro-
lysed their GTP to GDP. Once the terminal tubulin falls away, the next tubulin behind it, now
terminal, will fall away too and the whole microtubule will unravel until it either reaches
a zone that still has GTP or until new GTP-tubulins happen to cap an unravelling end. Left
to themselves, microtubules are therefore always either growing or collapsing catastroph-
ically; standing still is not an option. This state of affairs is called 'dynamic instability'.
45,46
The dynamic instability of microtubules can be modulated by microtubule-associated
proteins, and it is this modulation that enables the microtubule system to use adaptive
self-organization to construct itself into an optimum arrangement. In particular, '
þ
' end
þ
capping proteins can stabilize '
' ends and prevent their catastrophic collapse. Provided
that these capping proteins are located at sites that require connection to the microtubule
system and not elsewhere, the MTOC can nucleate microtubules at random and only those
that happen to reach appropriate targets will be stabilized. The correct microtubule anatomy
will therefore be created automatically, without the MTOC having to have any specific infor-
mation about the shape of the cell in which it finds itself.
For the tensegrity model to work, it is important that microtubules connect to the same
membrane structures to which microfilaments connect. If microtubules were not to reach
the membrane region at all, then tension in the microfilaments would cause the cell to collapse
inwards until the membrane reached the microtubules. If microtubules reached different parts
of the membrane, then the membrane would be expected to buckle, and perhaps to tear,
between the points of attachment of tension and compression elements. Fortunately, there is
ample evidence for microtubules being associated with cell-cell and cell-matrix junctions.
47
The microtubule system of cells, like the microfilament system, also seems to be respon-
sive to a changing mechanical load, although it is still not clear precisely what is being
sensed. In response to a number of experimental procedures designed to increase tension
in a specific part of a cell, microtubules become more numerous in that part of the cell.
48
These procedures include poking the cell with a pipette, stretching the matrix underneath
the cell, and holding back the body of cells that are migrating forwards. One thing that all of
these have in common is that, by applying an extra external force against which microfila-
ment tension can act, they would be expected to
reduce
the compression forces experienced
by the microtubules. This is because the matrix and the microtubules share the task of
resisting microfilament tension. In the same way that reducing the ability of microtubules
to resist compression, by depolymerizing them with drugs, increases the compressive
forces borne by the extracellular matrix,
8
increasing the compressive forces borne by the
matrix would be expected to decrease the compression in the microtubules (
Figure 5.11
).
It may, therefore, be that the increase in the number of tubules is a response to reduced
compression in the microtubule system rather than increased tension in the microfilaments.
It is not, however, clear why this should be required, although it is obvious that the
opposite relationship
d
increase in compression members being encouraged by increased
compression
d
would be bad for the cell because this positive feedback and that operating
on the microfilament system would couple to create runaway development of the cytoskel-
etal system in response to minor fluctuations in force.
