34,353 research outputs found
Physical constraints on accuracy and persistence during breast cancer cell chemotaxis
Directed cell motion in response to an external chemical gradient occurs in
many biological phenomena such as wound healing, angiogenesis, and cancer
metastasis. Chemotaxis is often characterized by the accuracy, persistence, and
speed of cell motion, but whether any of these quantities is physically
constrained by the others is poorly understood. Using a combination of theory,
simulations, and 3D chemotaxis assays on single metastatic breast cancer cells,
we investigate the links among these different aspects of chemotactic
performance. In particular, we observe in both experiments and simulations that
the chemotactic accuracy, but not the persistence or speed, increases with the
gradient strength. We use a random walk model to explain this result and to
propose that cells' chemotactic accuracy and persistence are mutually
constrained. Our results suggest that key aspects of chemotactic performance
are inherently limited regardless of how favorable the environmental conditions
are
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
- …