TY - JOUR
T1 - Endothelial cell migration on RGD-peptide-containing PEG hydrogels in the presence of sphingosine 1-phosphate
AU - Wacker, Bradley K.
AU - Alford, Shannon K.
AU - Scott, Evan A.
AU - Thakur, Meghna Das
AU - Longmore, Gregory D.
AU - Elbert, Donald L.
N1 - Funding Information:
We gratefully acknowledge funding from the Center for Materials Innovation at Washington University in St. Louis, from National Institutes of Health (NIH) training grant 5T32HL07916-05 (B.K.W., E.A.S., and S.K.A.), NIH R01CA85839 (G.D.L.), and NIH R01HL085364 (D.L.E.).
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Sphingosine 1-phosphate (S1P) is a potent chemokinetic agent for endothelial cells that is released by activated platelets. We previously developed Arg-Gly-Asp (RGD)-containing polyethylene glycol biomaterials for the controlled delivery of S1P to promote endothelialization. Here, we studied the effects of cell adhesion strength on S1P-stimulated endothelial cell migration in the presence of arterial levels of fluid shear stress, since an upward shift in optimal cell adhesion strengths may be beneficial for promoting long-term cell adhesion to materials. Two RGD peptides with different integrin-binding specificities were added to the polyethylene glycol hydrogels. A linear RGD bound primarily to β3 integrins, whereas a cyclic RGD bound through both β1 and β3 integrins. We observed increased focal adhesion formation and better long-term adhesion in flow with endothelial cells on linear RGD peptide, versus cyclic RGD, even though initial adhesion strengths were higher for cells on cyclic RGD. Addition of 100 nM S1P increased cell speed and random motility coefficients on both RGD peptides, with the largest increases found on cyclic RGD. For both peptides, much of the increase in cell migration speed was found for smaller cells (<1522 μm2 projected area), although the large increases on cyclic RGD were also due to medium-sized cells (2288-3519 μm2). Overall, a compromise between high cell migration rates and long-term adhesion will be important in the design of materials that endothelialize after implantation.
AB - Sphingosine 1-phosphate (S1P) is a potent chemokinetic agent for endothelial cells that is released by activated platelets. We previously developed Arg-Gly-Asp (RGD)-containing polyethylene glycol biomaterials for the controlled delivery of S1P to promote endothelialization. Here, we studied the effects of cell adhesion strength on S1P-stimulated endothelial cell migration in the presence of arterial levels of fluid shear stress, since an upward shift in optimal cell adhesion strengths may be beneficial for promoting long-term cell adhesion to materials. Two RGD peptides with different integrin-binding specificities were added to the polyethylene glycol hydrogels. A linear RGD bound primarily to β3 integrins, whereas a cyclic RGD bound through both β1 and β3 integrins. We observed increased focal adhesion formation and better long-term adhesion in flow with endothelial cells on linear RGD peptide, versus cyclic RGD, even though initial adhesion strengths were higher for cells on cyclic RGD. Addition of 100 nM S1P increased cell speed and random motility coefficients on both RGD peptides, with the largest increases found on cyclic RGD. For both peptides, much of the increase in cell migration speed was found for smaller cells (<1522 μm2 projected area), although the large increases on cyclic RGD were also due to medium-sized cells (2288-3519 μm2). Overall, a compromise between high cell migration rates and long-term adhesion will be important in the design of materials that endothelialize after implantation.
UR - http://www.scopus.com/inward/record.url?scp=37749039764&partnerID=8YFLogxK
U2 - 10.1529/biophysj.107.109074
DO - 10.1529/biophysj.107.109074
M3 - Article
C2 - 17827231
AN - SCOPUS:37749039764
SN - 0006-3495
VL - 94
SP - 273
EP - 285
JO - Biophysical Journal
JF - Biophysical Journal
IS - 1
ER -