Dynamic contact forces on leukocyte microvilli and their penetration of the endothelial glycocalyx

We develop a theoretical model to examine the combined effect of gravity an d microvillus length heterogeneity on tip contact force (F-z(m)) during fre e rolling in vitro, including the initiation of L-, P-, and E-selectin teth ers and the threshold behavior at low shear. P-z(m) grows nonlinearly with shear. At shear stress of 1 dyn/cm(2), F-z(m) is one to two orders of magni tude 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 sub strate; hence at the shear threshold (0.4 dyn/cm(2) 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 t hen applied in vivo to explore,the free-rolling interaction of leukocyte mi crovilli with endothelial glycocalyx and the necessary conditions for glyco calyx penetration to initiate cell rolling. The model predicts that for art eriolar capillaries even the longest microvilli cannot initiate rolling, ex cept in regions of low shear or flow reversal. In postcapillary venules, wh ere shear stress is similar to2 dyn/cm(2), tethering interactions are highl y likely, provided that there are some relatively long microvilli. Once tet hering is initiated, rolling tends to ensue because F-m(z) and contact dura tion will both increase substantially to facilitate glycocalyx penetration by the shorter microvilli.