Abstract
The crawling movement of cells in response to a
chemoattractant gradient is a complex process requiring coordination of various
subcellular activities. Although a complete description of the mechanisms
underlying cell movement remains elusive, the very first step of
gradient sensing, enabling the cell to perceive the imposed gradient, is
becoming more transparent. The increased understanding of this step has
been driven by the discovery that within 5-10 s of applying a weak
chemoattractant gradient, membrane phosphoinositides such as PIP(3)
localize at the front end of the cell. It is currently believed that the
gradient sensing mechanism is precisely the mechanism leading to
this localization. We have formulated a reaction-diffusion model
based on the phosphoinositide cycle which predicts various responses
of motile cells in addition to the phosphoinositide polarization
induced by chemoattractant gradients. The responses include: (a)
Polarized sensitivity wherein a polarized cell responds to a change in
the direction of the gradient by turning its existing front. (b)
Spontaneous polarization wherein cells polarize in a random direction
even if the surrounding chemoattractant concentration is uniform.
(c) Unique localization which refers to the formation of a unique
polarity even in the face of multiple chemoattractant sources. The above
responses preclude the hypothesis that the cell merely amplifies the
external signal. Our model indicates that the cell must be viewed as a
system that nonlinearly processes chemoattractant inputs. We show in
particular that these seemingly complex dynamics can be explained
very simply in terms of the instabilities and wavefront dynamics
that are characteristic of the activator-inhibitor class of models.
- 15363929
- animals,
- apparatus,
- biological,
- cell
- cells,
- centrifugation,
- chemotaxis,
- culture
- endoplasmic
- eukaryotic
- factor-2,
- fluorescence,
- fractions,
- golgi
- humans,
- initiation
- interfering,
- microscopy,
- models,
- movement,
- oligonucleotides,
- phosphatidylinositols,
- phosphorothioate
- reticulum,
- rna,
- small
- subcellular
- techniques,
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