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Monocyte recruitment to endothelial cells in response to oscillatory shear stress

TZUNG K. HSIAI^,1, SUNG K. CHO, PAK K. WONG, MIKE ING, ADLER SALAZAR, ALEX SEVANIAN, MOHAMAD NAVAB^*, LINDA L. DEMER^* and CHIH-MING HO

Department of Biomedical Engineering and Division of Cardiovascular Medicine, USC School of Engineering and Keck School of Medicine, Los Angeles;
Department of Mechanical and Aerospace Engineering, UCLA School of Engineering and Applied Sciences, Los Angeles;
^* Division of Cardiology, Department of Medicine, UCLA School of Medicine, Los Angeles; and
Department of Molecular Pharmacology & Toxicology, USC School of Pharmacy, Los Angeles, California, USA

¹Correspondence: University of Southern California, Olin Hall of Engineering 500, Los Angeles, CA 90089-1451, USA. E-mail: hsiai{at}usc.edu

Leukocyte recruitment to endothelial cells is a critical event in inflammatory responses. The spatial, temporal gradients of shear stress, topology, and outcome of cellular interactions that underlie these responses have so far been inferred from static imaging of tissue sections or studies of statically cultured cells. In this report, we developed micro-electromechanical systems (MEMS) sensors, comparable to a single endothelial cell (EC) in size, to link real-time shear stress with monocyte/EC binding kinetics in a complex flow environment, simulating the moving and unsteady separation point at the arterial bifurcation with high spatial and temporal resolution. In response to oscillatory shear stress () at ± 2.6 dyn/cm² at a time-averaged shear stress (_ave)=0 and 0.5 Hz, individual monocytes displayed unique to-and-fro trajectories undergoing rolling, binding, and dissociation with other monocyte, followed by solid adhesion on EC. Our study quantified individual monocyte/EC binding kinetics in terms of displacement and velocity profiles. Oscillatory flow induces up-regulation of adhesion molecules and cytokines to mediate monocyte/EC interactions over a dynamic range of shear stress ± 2.6 dyn/cm² (P=0.50, n=10).—Hsiai, T. K., Cho, S. K., Wong, P. K., Ing, M., Salazar, A., Sevanian, A., Navab, M., Demer, L. L., Ho, C.-M. Monocyte recruitment to endothelial cells in response to oscillatory shear stress.

Key Words: micro-electromechanical systems (MEMS) • cell tracking velocimetry • shear stress sensors • endothelial cells • monocytes

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