Biophys J, March 2001, p. 1124-1140, Vol. 80, No. 3

Dynamic Contact Forces on Leukocyte Microvilli and Their Penetration of the Endothelial Glycocalyx

Yihua Zhao,^* Shu Chien,^* and Sheldon Weinbaum

 ^*Department of Bioengineering and the Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, California 92093; and  Center for Biomedical Engineering and Department of Mechanical Engineering, CUNY Graduate School and City College of New York, New York, New York 10031 USA

We develop a theoretical model to examine the combined effect of gravity and microvillus length heterogeneity on tip contact force (F) during free rolling in vitro, including the initiation of L-, P-, and E-selectin tethers and the threshold behavior at low shear. F grows nonlinearly with shear. At shear stress of 1 dyn/cm², F is one to two orders of magnitude greater than the 0.1 pN force for gravitational settling without flow. At shear stresses >0.2 dyn/cm² only the longest microvilli contact the substrate; hence at the shear threshold (0.4 dyn/cm² for L-selectin), only 5% of microvilli can initiate tethering interaction. The characteristic time for tip contact is surprisingly short, typically 0.1-1 ms. This model is then applied in vivo to explore the free-rolling interaction of leukocyte microvilli with endothelial glycocalyx and the necessary conditions for glycocalyx penetration to initiate cell rolling. The model predicts that for arteriolar capillaries even the longest microvilli cannot initiate rolling, except in regions of low shear or flow reversal. In postcapillary venules, where shear stress is ~2 dyn/cm², tethering interactions are highly likely, provided that there are some relatively long microvilli. Once tethering is initiated, rolling tends to ensue because F and contact duration will both increase substantially to facilitate glycocalyx penetration by the shorter microvilli.

Biophys J, March 2001, p. 1124-1140, Vol. 80, No. 3
© 2001 by the Biophysical Society   0006-3495/01/03/1124/17  $2.00

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