Cyclic changes in keratocyte speed and traction stress arise from Ca2+-dependent regulation of cell adhesiveness.
The activation of stretch-activated calcium channels (SACs) in keratocytes can induce spatially coordinated increases in traction stress that promote protrusion at the cell front, while simultaneously inducing retraction at the rear. To investigate how this occurs, we correlated calcium-induced changes in traction stress with alterations in cell speed and shape. Cyclic changes in these parameters were associated with each calcium transient. In addition, an inverse relationship was found between traction stress and cell speed, suggesting that alternating changes in adhesiveness were occurring at the rear. We investigated this further by inhibiting or inducing calcium transients and observing the effects on traction stress, cell speed and shape. Inhibition of calcium transients prevented retraction and led to a slow increase in traction stress. In addition, large aggregates of vinculin developed at the lateral rear edges of treated keratocytes, consistent with an increase in adhesiveness. Induction of a calcium transient resulted in a rapid retraction, involving both increased traction stress and adhesion disassembly at the rear. We also found that keratocytes exhibiting frequent transients generated larger traction stress and moved significantly faster than other cells. Together, these data suggest that calcium transients coordinate changes in adhesiveness with SAC-mediated cycles of mechano-chemical feedback.
Doyle
Andrew D
AD
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Lee
Juliet
J
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology; D010507:Periodicity; D011036:Poecilia; D013314:Stress, Mechanical; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000001:Calcimycin; D004533:Egtazic Acid; D005682:Gadolinium; D002118:Calcium