58 research outputs found
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
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
Periodic migration in a physical model of cells on micropatterns
We extend a model for the morphology and dynamics of a crawling eukaryotic
cell to describe cells on micropatterned substrates. This model couples cell
morphology, adhesion, and cytoskeletal flow in response to active stresses
induced by actin and myosin. We propose that protrusive stresses are only
generated where the cell adheres, leading to the cell's effective confinement
to the pattern. Consistent with experimental results, simulated cells exhibit a
broad range of behaviors, including steady motion, turning, bipedal motion, and
periodic migration, in which the cell crawls persistently in one direction
before reversing periodically. We show that periodic motion emerges naturally
from the coupling of cell polarization to cell shape by reducing the model to a
simplified one-dimensional form that can be understood analytically.Comment: 15 pages (includes supplementary material as an appendix). Recently
accepted to Physical Review Letter
Physical limits on galvanotaxis
Eukaryotic cells can polarize and migrate in response to electric fields via
"galvanotaxis," which aids wound healing. Experimental evidence suggests cells
sense electric fields via molecules on the cell's surface redistributing via
electrophoresis and electroosmosis, though the sensing species has not yet been
conclusively identified. We develop a model that links sensor redistribution
and galvanotaxis using maximum likelihood estimation. Our model predicts a
single universal curve for how galvanotactic directionality depends on field
strength. We can collapse measurements of galvanotaxis in keratocytes, neural
crest cells, and granulocytes to this curve, suggesting that stochasticity due
to the finite number of sensors may limit galvanotactic accuracy. We find cells
can achieve experimentally observed directionalities with either a few (~100)
highly-polarized sensors, or many (~10,000) sensors with a ~6-10% change in
concentration across the cell. We also identify additional signatures of
galvanotaxis via sensor redistribution, including the presence of a tradeoff
between accuracy and variance in cells being controlled by rapidly switching
fields. Our approach shows how the physics of noise at the molecular scale can
limit cell-scale galvanotaxis, providing important constraints on sensor
properties, and allowing for new tests to determine the specific molecules
underlying galvanotaxis
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