Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling.

Abstract:

:It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Weiger MC,Ahmed S,Welf ES,Haugh JM

doi

10.1016/j.bpj.2009.09.051

subject

Has Abstract

pub_date

2010-01-06 00:00:00

pages

67-75

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)01565-3

journal_volume

98

pub_type

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