Fluid shear stress modulates cell migration induced by sphingosine 1-phosphate and vascular endothelial growth factor.
The rational design of drug delivery systems requires the ability to predict the environment-specific responses of target cells to the delivered drug. Here we describe the in vitro effects of fluid shear stress, vascular endothelial growth factor (VEGF), and sphingosine 1-phosphate (S1P) on the migration of human umbilical vein endothelial cells (HUVEC). Endothelial cell migration into a scrape wound was enhanced in S1P- or VEGF-stimulated HUVEC by the addition of fluid shear stress. In both cases, scrape wound closure rates were near a maximal value that was not exceeded when cells were exposed to all three factors. We also found that cell migration into a scrape wound due to S1P stimulation was correlated with the S1P1 mRNA concentration, in systems where cell migration was not already near maximal. The present work represents our initial steps toward predicting cell migration based upon the activation state of the receptors and enzymes involved in the chemokinetic response. These results also illustrate the importance of context-dependent analysis of cell signaling cascades.
Hughes
Shannon K
SK
Department of Biomedical Engineering and Center for Materials Innovation, Washington University in St. Louis, Box 1097, St. Louis, MO 63130, USA.
Wacker
Bradley K
BK
Kaneda
Megan M
MM
Elbert
Donald L
DL
D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology
D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; D042442:Vascular Endothelial Growth Factors; C060506:sphingosine 1-phosphate; D013110:Sphingosine