134 research outputs found
Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance
Single eukaryotic cells commonly sense and follow chemical gradients,
performing chemotaxis. Recent experiments and theories, however, show that even
when single cells do not chemotax, clusters of cells may, if their interactions
are regulated by the chemoattractant. We study this general mechanism of
"collective guidance" computationally with models that integrate stochastic
dynamics for individual cells with biochemical reactions within the cells, and
diffusion of chemical signals between the cells. We show that if clusters of
cells use the well-known local excitation, global inhibition (LEGI) mechanism
to sense chemoattractant gradients, the speed of the cell cluster becomes
non-monotonic in the cluster's size - clusters either larger or smaller than an
optimal size will have lower speed. We argue that the cell cluster speed is a
crucial readout of how the cluster processes chemotactic signal; both
amplification and adaptation will alter the behavior of cluster speed as a
function of size. We also show that, contrary to the assumptions of earlier
theories, collective guidance does not require persistent cell-cell contacts
and strong short range adhesion to function. If cell-cell adhesion is absent,
and the cluster cohesion is instead provided by a co-attraction mechanism, e.g.
chemotaxis toward a secreted molecule, collective guidance may still function.
However, new behaviors, such as cluster rotation, may also appear in this case.
Together, the combination of co-attraction and adaptation allows for collective
guidance that is robust to varying chemoattractant concentrations while not
requiring strong cell-cell adhesion.Comment: This article extends some results previously presented in
arXiv:1506.0669
How input fluctuations reshape the dynamics of a biological switching system
An important task in quantitative biology is to understand the role of
stochasticity in biochemical regulation. Here, as an extension of our recent
work [Phys. Rev. Lett. 107, 148101 (2011)], we study how input fluctuations
affect the stochastic dynamics of a simple biological switch. In our model, the
on transition rate of the switch is directly regulated by a noisy input signal,
which is described as a nonnegative mean-reverting diffusion process. This
continuous process can be a good approximation of the discrete birth-death
process and is much more analytically tractable. Within this new setup, we
apply the Feynman-Kac theorem to investigate the statistical features of the
output switching dynamics. Consistent with our previous findings, the input
noise is found to effectively suppress the input-dependent transitions. We show
analytically that this effect becomes significant when the input signal
fluctuates greatly in amplitude and reverts slowly to its mean.Comment: 7 pages, 4 figures, submitted to Physical Review
Emergent collective chemotaxis without single-cell gradient sensing
Many eukaryotic cells chemotax, sensing and following chemical gradients.
However, experiments have shown that even under conditions when single cells
cannot chemotax, small clusters may still follow a gradient. This behavior has
been observed in neural crest cells, in lymphocytes, and during border cell
migration in Drosophila, but its origin remains puzzling. Here, we propose a
new mechanism underlying this "collective guidance", and study a model based on
this mechanism both analytically and computationally. Our approach posits that
the contact inhibition of locomotion (CIL), where cells polarize away from
cell-cell contact, is regulated by the chemoattractant. Individual cells must
measure the mean attractant value, but need not measure its gradient, to give
rise to directional motility for a cell cluster. We present analytic formulas
for how cluster velocity and chemotactic index depend on the number and
organization of cells in the cluster. The presence of strong orientation
effects provides a simple test for our theory of collective guidance.Comment: Updated with additional simulations. Aspects of v1 of this paper
about adaptation and amplification have been extended and turned into a
separate paper, and removed from the current versio
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