Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks.
Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduction network, as well as actin polymerization. Similarly to chemoattractants, the shear flow-induced signal transduction events displayed features of excitability, including the ability to mount a full response irrespective of the length of the stimulation and a refractory period that is shared with that generated by chemoattractants. Loss of G protein subunits, inhibition of multiple signal transduction events, or disruption of calcium signaling attenuated the response to acute mechanical stimulation. Unlike the response to chemoattractants, an intact actin cytoskeleton was essential for reacting to mechanical perturbation. These results taken together suggest that chemotactic and mechanical stimuli trigger activation of a common signal transduction network that integrates external cues to regulate cytoskeletal activity and drive cell migration.
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; pnd@jhmi.edu yulia.artemenko@oswego.edu.
Yulia
Y
Artemenko
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Lucas
L
Axiotakis
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Jane
J
Borleis
Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD 21218.
Pablo A
PA
Iglesias
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; pnd@jhmi.edu yulia.artemenko@oswego.edu.
Peter N
PN
Devreotes
D008841:Actin Cytoskeleton / Q000235:genetics*; D020013:Calcium Signaling; D002465:Cell Movement; D002630:Chemotactic Factors / Q000494:pharmacology*; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000187:drug effects; D017125:Genes, Protozoan; D015398:Signal Transduction; D013314:Stress, Mechanical
D002630:Chemotactic Factors; D019204:GTP-Binding Proteins
biochemical excitability; biomechanics; inflammation; motility; shear stress