TY - JOUR
T1 - Fluid shear regulates the kinetics and molecular mechanisms of activation-dependent platelet binding to colon carcinoma cells
AU - McCarty, Owen J.T.
AU - Jadhav, Sameer
AU - Burdick, Monica M.
AU - Bell, William R.
AU - Konstantopoulos, Konstantinos
N1 - Funding Information:
This work was supported by a Whitaker Foundation and a DuPont Young Professor grants.
PY - 2002
Y1 - 2002
N2 - This study was undertaken to investigate the kinetics and molecular requirements of platelet binding to tumor cells in bulk suspensions subjected to a uniform linear shear field, using a human colon adenocarcinoma cell line (LS174T) as a model. The effects of shear rate (20-1000 s-1), shear exposure time (30-300 s), shear stress (at constant shear rate by adjusting the viscosity of the medium from 1.3-2.6 cP), cell concentration, and platelet activation on platelet-LS174T heteroaggregation were assessed. The results indicate that hydrodynamic shear-induced collisions augment platelet-LS174T binding, which is further potentiated by thrombin/GPRP-NH2. Peak adhesion efficiency occurs at low shear and decreases with increasing shear. Intercellular contact duration is the predominant factor limiting heteroaggregation at shear rates up to 200 s-1, whereas these interactions become shear stress-sensitive at ≥400 s-1. Heteroaggregation increases with platelet concentration due to an elevation of the intercellular collision frequency, whereas adhesion efficiency remains nearly constant. Moreover, hydrodynamic shear affects the receptor specificity of activation-dependent platelet binding to LS174T cells, as evidenced by the transition from a P-selectin-independent/Arg-Gly-Asp (RGD)-dependent process at 100 s-1 to a P-selectin/ αIIbβ3-dependent interaction at 800 s-1. This study demonstrates that platelet activation and a fluid-mechanical environment representative of the vasculature affect platelet-tumor cell adhesive interactions pertinent to the process of blood-borne metastasis.
AB - This study was undertaken to investigate the kinetics and molecular requirements of platelet binding to tumor cells in bulk suspensions subjected to a uniform linear shear field, using a human colon adenocarcinoma cell line (LS174T) as a model. The effects of shear rate (20-1000 s-1), shear exposure time (30-300 s), shear stress (at constant shear rate by adjusting the viscosity of the medium from 1.3-2.6 cP), cell concentration, and platelet activation on platelet-LS174T heteroaggregation were assessed. The results indicate that hydrodynamic shear-induced collisions augment platelet-LS174T binding, which is further potentiated by thrombin/GPRP-NH2. Peak adhesion efficiency occurs at low shear and decreases with increasing shear. Intercellular contact duration is the predominant factor limiting heteroaggregation at shear rates up to 200 s-1, whereas these interactions become shear stress-sensitive at ≥400 s-1. Heteroaggregation increases with platelet concentration due to an elevation of the intercellular collision frequency, whereas adhesion efficiency remains nearly constant. Moreover, hydrodynamic shear affects the receptor specificity of activation-dependent platelet binding to LS174T cells, as evidenced by the transition from a P-selectin-independent/Arg-Gly-Asp (RGD)-dependent process at 100 s-1 to a P-selectin/ αIIbβ3-dependent interaction at 800 s-1. This study demonstrates that platelet activation and a fluid-mechanical environment representative of the vasculature affect platelet-tumor cell adhesive interactions pertinent to the process of blood-borne metastasis.
UR - http://www.scopus.com/inward/record.url?scp=0035997017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035997017&partnerID=8YFLogxK
U2 - 10.1016/S0006-3495(02)75212-0
DO - 10.1016/S0006-3495(02)75212-0
M3 - Article
C2 - 12124268
AN - SCOPUS:0035997017
SN - 0006-3495
VL - 83
SP - 836
EP - 848
JO - Biophysical Journal
JF - Biophysical Journal
IS - 2
ER -