Abstract
Tumor cell adhesion to vessel walls in the microcirculation is one critical step in cancer metastasis. In this paper, the hypothesis that tumor cells prefer to adhere at the microvessels with localized shear stresses and their gradients, such as in the curved microvessels, was examined both experimentally and computationally. Our in vivo experiments were performed on the microvessels (post-capillary venules, 30–50 μm diameter) of rat mesentery. A straight or curved microvessel was cannulated and perfused with tumor cells by a glass micropipette at a velocity of ~1mm/s. At less than 10 min after perfusion, there was a significant difference in cell adhesion to the straight and curved vessel walls. In 60 min, the averaged adhesion rate in the curved vessels (n = 14) was ~1.5-fold of that in the straight vessels (n = 19). In 51 curved segments, 45% of cell adhesion was initiated at the inner side, 25% at outer side, and 30% at both sides of the curved vessels. To investigate the mechanical mechanism by which tumor cells prefer adhering at curved sites, we performed a computational study, in which the fluid dynamics was carried out by the lattice Boltzmann method , and the tumor cell dynamics was governed by the Newton’s law of translation and rotation. A modified adhesive dynamics model that included the influence of wall shear stress/gradient on the association/dissociation rates of tumor cell adhesion was proposed, in which the positive wall shear stress/gradient jump would enhance tumor cell adhesion while the negative wall shear stress/gradient jump would weaken tumor cell adhesion. It was found that the wall shear stress/gradient, over a threshold, had significant contribution to tumor cell adhesion by activating or inactivating cell adhesion molecules. Our results elucidated why the tumor cell adhesion prefers to occur at the positive curvature of curved microvessels with very low Reynolds number (in the order of 10−2) laminar flow.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alon R, Hammer DA, Springer TA (1995) Lifetime of the P-selectin Carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374: 539–542
Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200: 618–627
Bongrand P, Bell GI (1984) Cell-cell adhesion: parameters and possible mechanisms. In: Perelson A, DeLisi C, Wiegel FW (eds) Cell surface dynamics: concepts andmodels. Marcel Dekker, NewYork
Caputo KE, Hammer DA (2005) Effect of microvillus deformability on leukocyte adhesion explored using adhesive dynamics simulations. Biophys J 89: 187–200
Chang KC, Hammer DA (1996) Influence of direction and type of applied force on the detachment of macromolecularly-bound particles from surfaces. Langmuir 12: 2271–2282
Chang KC, Tees DFJ, Hammer DA (2000) The state diagram for cell adhesion under flow: leukocyte rolling and firm adhesion. PNAS 97: 11262–11267
Chen S, Doolen GD (1998) Lattice Boltzmann method for fluid flows. Annu Rev Fluid Mech 30: 329–364
Dong C, Cao J, Struble EJ, Lipowksy HH (1999) Mechanics of leukocyte deformation and adhesion to endothelium in shear flow. Ann Biomed Eng 27: 298–312
Dong C, Slattery M, Liang SL (2005) Micromechanics of tumor cell adhesion and migration under dynamic flow conditions. Frontiers Biosci 10: 379–384
Fu BM, Shen S (2004) Acute VEGF effect on solute permeability of mammalian microvessels in vivo. Microvasc Res 68: 51–62
Haier J, Nicolson GL (2001) Tumor cell adhesion under hydrodynamic conditions of fluid flow. APMIS 109: 241–262
Hammer DA, Apte SM (1992) Simulation of cell rolling and adhesion on surfaces in shear flow: general results and analysis of selectin-mediated neutrophil adhesion. Biophys J 63: 35–57
Ladd ACJ (1994) Numerical simulation of particulate suspensions via a discretized Boltzmann equation. J Fluid Mech 271: 285–309
Liu Q, Mirc D, Fu BM (2008) Mechanical mechanisms of thrombosis in intact bent microvessels of rat mesentery. J Biomech 41: 2726–2734
Lomakina EB, Waugh RE (2004) Micromechanical tests of adhesion dynamics between neutrophils and immobilized iCAM-1. Biophys J 86: 1223–1233
Migliorini C, Qian YH, Chen HD, Brown EB, Jain RK, Munn LL (2002) Red blood cells augment leukocyte rolling in a virtual blood vessel. Biophys J 83: 1834–1841
Munn LL, Melder RJ, Jain RK (1996) Role of erythrocytes in leukocyte-endothelial interactions: mathematical model and experimental validation. Biophys J 71: 466–478
Shen S, Fan J, Cai B, Lv Y, Zeng M, Hao Y, Giancotti F, Fu BM (2010) Vascular endothelial growth factor enhances mammary cancer cell adhesion to endothelium in vivo. J Exp Physiol 95: 369–379
Skalak R, Chien S (1987) Handbook of bioengineering. McGraw-Hill, New York
Sun CH, Migliorini C, Munn LL (2003) Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice Boltzmann analysis. Biophys J 85: 208–222
Weiss L (1992) Biomechanical interactions of cancer-cells with the microvasculature during hematogenous metastasis. Cancer Metastasis Rev 11: 227–235
Yan WW, Liu Y, Fu BM (2010) Effects of curvature and cell-cell interaction on cell adhesion in microvessels. Biomech Model Mechanobiol 9: 629–640
Zhu C (2000) Kinetics and mechanics of cell adhesion. J Biomech 33: 23–33
Zhu C, Bao G, Wang N (2000) Cell mechanics: mechanical response, cell adhesion, and molecular deformation. Annu Rev Biomed Eng 2: 189–226
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yan, W.W., Cai, B., Liu, Y. et al. Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels. Biomech Model Mechanobiol 11, 641–653 (2012). https://doi.org/10.1007/s10237-011-0339-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10237-011-0339-6