Biology Reference
In-Depth Information
actin branches and increasing the activity of Rho-mediated polymerization of contactile
actin-myosin filaments that give trailing rather than leading edge character to the cell cortex
(
Figure 9.10
).
MULTIPLE SOURCES OF CHEMOREPELLANT CAN DEFINE
A PATHWAY IN A WAY THAT MULTIPLE SOURCES OF
CHEMOATTRACTANT CANNOT
Cells and growth cones steer away from sources of chemorepellants. If they are in an area
of the embryo in which multiple sources of chemorepellants exist, then (in the absence of any
additional cues) migrating cells will avoid them all by keeping to a pathway defined by the
local minimum in the concentration field. Two extended sources can define a path in two-
dimensional space (cells constrained to migrate on a flat sheet of matrix are, effectively, in
two-dimensional space) while three extended sources can define a unique path in three-
dimensional space. Because the 'force' of repulsion rises if a cell blunders nearer the source,
the system provides rapid feedback to correct the course of the cell and the guidance system
is stable.
It might be supposed at first glance that multiple sources of chemoattractant could also
define a pathway, a cell being unwilling to go towards one source of attractant because
such an action would take it further from the others. Such a system would only be stable
if the attraction of a place increased the further a cell strayed from it (for example, as if the
cell were attached to that place with a mechanical spring). In chemotaxis, the 'force' of attrac-
tion is a function of the concentration gradient, which reduces as the cell moves further away.
The equilibrium of a cell between two sources is therefore inherently unstable, and if the cell
strays even slightly towards one source, the attraction of that source increases while that of
the rival sources decreases; the cell has been captured. Attractive and repulsive systems are
not, therefore, equivalent in their abilities
d
surround-repulsion can define pathways in
a way that attraction cannot.
THE USEFULNESS OF NOISE TO DECISION-MAKING BY MIGRATING
CELLS
The activity at the leading edge of the cell, while regulated to some extent by external
signals, also reflects moment-to-moment fluctuations in local concentrations of key compo-
nents and of the chance nucleation of actin branching, actin severance, and so on. The prob-
abilities of activations, nucleations and cuttings are biased by signalling pathways but are
still subject to random fluctuations of thermodynamic origin. In other words, the system is
'noisy'. Noise is often thought of as an enemy of order and a potential nuisance to be elim-
inated as much as possible from any good control system. It is a very useful attribute of cell
navigation, however, because it protects a migrating cell from the fatal indecision of
Buriden's Ass (an apocryphal animal which, finding itself located equidistantly from two
sources of sustenance, was drawn equally to both, so remained where it was and starved).
Even if a cell is, for a moment, placed exactly between two equally strong sources of
