Biology Reference
In-Depth Information
mimics the attachment of the bead to a substrate. Under these conditions, the growth cone
pulls on the bead, bending the needle a little, and then begins to extend and to steer in the
direction of the bead.
8
This is precisely what would be expected of true haptotaxis.
DUROTAXIS: GUIDANCE OF CELLS BY GRADIENTS
OF MECHANICAL COMPLIANCE
Durotaxis,
)
the ability of cells to navigate according to the stiffness of their substrate, is
closely related to haptotaxis because substrate flexibility is related to the ability of an adhe-
sion to bear mechanical force. When cells are cultured on substrates that are chemically iden-
tical but have different mechanical flexibilities, their rate of migration alters so that they
migrate more and faster on stiffer substrates.
10
If a cell were to find itself straddling the
boundary between substrates of different flexibilities, one would therefore expect it to
migrate on to the stiffer one, since the part of its leading edge on the stiffer one would
show the stronger migratory response. If this is true of a boundary, then it should also be
true of a steady gradient.
Substrates with a gradient of rigidity (Young's Modulus) varying from 14 kN/m
2
to
30 kN/m
2
can be made by making a polyacrylamide 'gradient gel' with a constant amount
of acrylamide but a varying amount of bis-acrylamide cross-linker. When coated evenly with
collagen, such gels are suitable substrates for fibroblasts. Cells plated on to such a substrate
migrate towards the stiffer substrate, as long as they are few enough that deformations of the
substrate by the other cells do not confuse the situation.
11
The mechanism of durotaxis may be entirely mechanical and explicable in terms of how
well a section of leading edge can push and pull on the substrate without it 'wasting' their
force by deforming under them, or by active processing of information from biochemical
transduction of sensed forces. Although there has been too little work done on the phenom-
enon for a general mechanism to be agreed with much confidence, there are two reasons to
speculate that active signal processing is involved. The first reason is based mainly on nega-
tive reasoning: current mathematical models of purely mechanical durotaxis
12
predict that it
should be sensitive to the absolute value of stiffness, not just to the gradient. Careful study of
the behaviour of vascular smooth muscle cells on a substrate of graded stiffness (from 1 to
4 kN/m
2
over 0.1 mm) demonstrates that, while cell morphology does depend on absolute
stiffness, durotaxis and orientation is controlled by the steepness of the gradient but not
the absolute stiffness at any point.
13
Drawing a firm conclusion from this kind of argument
is, however, dangerous as it relies on the quality of the model. The second reason to suspect
that active processing of sensed stiffness information may be involved in durotaxis is the
discovery that systems do exist for relaying stiffness information in to cytoplasmic signal
transduction pathways. The sensors include RTPT
a
and integrins, and the signal probably
proceeds via SRC family kinases.
14
Again, this evidence is merely suggestive: the signals
might be used instead for some other purpose unconnected with movement and it is already
known that stiffness can control stem cell differentiation.
15
)
A word of mixed linguistic parentage from the Latin
durus
arrangement. It
was coined by the researchers who first made the graded substrates described in this section.
9
¼
hard, and the Greek
taxis
¼
