The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling.
The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling.
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DOI：
10.1083/jcb.138.5.1169
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发表时间：
1997-09-08
期刊：
影响因子：
--
通讯作者：
Springer TA
中科院分区：
文献类型：
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作者：
Alon R;Chen S;Puri KD;Finger EB;Springer TA
已经提出了两种机制来调节选择素的滚动速度。它们是（a）键解离的内在动力学，和（b）反应顺应性，即键解离反应对施加力的敏感性。为了确定这些机制中的哪一个可以解释 L-选择素上的白细胞滚动速度比 E-和 P-选择素上的白细胞滚动速度快 7.5-11.5 倍，我们通过检查瞬时系链的解离来比较这三种选择素。我们发现 L-选择素的系链键解离的内在动力学比 E-和 P-选择素快 7-10 倍，并且与通过这些选择素的滚动速度成正比。滚动过程中暂停的持续时间对应于低密度基底上瞬态系链的持续时间。此外，与E-和P-选择素相比，施加的力对L-选择素的解离动力学的增加较小，这表明反应顺应性并不是导致L-选择素更快滚动的原因。进一步的测量为理解滚动的分子基础提供了生物化学和生物物理框架。流动反向期间系留细胞的位移以及滚动期间连续暂停之间的距离的测量提供了系链长度和粘合剂接触区长度的估计，并表明每个接触区仅用两条系链就发生滚动。系链键寿命是键上力的指数函数，并且系链键弹簧常数的上限与凝集素-EGF单元的估计弹性弹簧常数具有相同的数量级。剪切独特地提高了 L-选择素瞬时系链形成的速率，以及系链转化为滚动粘附的速率，从而进一步了解通过 L-选择素滚动的剪切阈值要求。
Two mechanisms have been proposed for regulating rolling velocities on selectins. These are (a) the intrinsic kinetics of bond dissociation, and (b) the reactive compliance, i.e., the susceptibility of the bond dissociation reaction to applied force. To determine which of these mechanisms explains the 7.5–11.5-fold faster rolling of leukocytes on L-selectin than on E- and P-selectins, we have compared the three selectins by examining the dissociation of transient tethers. We find that the intrinsic kinetics for tether bond dissociation are 7–10-fold more rapid for L-selectin than for E- and P-selectins, and are proportional to the rolling velocities through these selectins. The durations of pauses during rolling correspond to the duration of transient tethers on low density substrates. Moreover, applied force increases dissociation kinetics less for L-selectin than for E- and P-selectins, demonstrating that reactive compliance is not responsible for the faster rolling through L-selectin. Further measurements provide a biochemical and biophysical framework for understanding the molecular basis of rolling. Displacements of tethered cells during flow reversal, and measurements of the distance between successive pauses during rolling provide estimates of the length of a tether and the length of the adhesive contact zone, and suggest that rolling occurs with as few as two tethers per contact zone. Tether bond lifetime is an exponential function of the force on the bond, and the upper limit for the tether bond spring constant is of the same order of magnitude as the estimated elastic spring constant of the lectin–EGF unit. Shear uniquely enhances the rate of L-selectin transient tether formation, and conversion of tethers to rolling adhesions, providing further understanding of the shear threshold requirement for rolling through L-selectin.