MOLECULAR MECHANISMS DETERMINING THE STRENGTH OF RECEPTOR-MEDIATED INTERMEMBRANE ADHESION
MOLECULAR MECHANISMS DETERMINING THE STRENGTH OF RECEPTOR-MEDIATED INTERMEMBRANE ADHESION
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DOI：
10.1016/s0006-3495(95)79990-8
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发表时间：
1995-09-01
影响因子：
3.4
通讯作者：
RINGSDORF, H
中科院分区：
文献类型：
--
作者：
LECKBAND, D;MULLER, W;RINGSDORF, H
受体介导的细胞粘附的强度直接受细胞表面和底层基质之间的内聚破坏机制控制。解结合可以发生在特定键的位点处或双层内，这导致疏水锚从膜内部撕裂。在这项工作中，表面力装置已被用来调查受体-配体键的亲和力和受体耦合膜分离的主导机制之间的关系。本研究中使用的受体和配体分别是膜结合的链霉亲和素和生物素类似物，溶液亲和力范围超过10个数量级。利用表面力仪的光学技术，直接观察了膜破裂的发生。后者的观察结果与相应的膜间粘附强度的测量一起用于确定每个链霉亲和素类似物对的主要失效途径。即使在膜的拔出能量超过平衡结合能的情况下，内聚失效发生在膜内部几乎所有的键亲和力考虑。这些结果与以前的研究结果是一致的，并提供了直接支持的普遍持有的观点，即在非平衡条件下施加的外部应力，梯度的键能，而不是平衡键能单独，确定的粘合强度。此外，我们的研究结果直接表明，在存在竞争失效机制的情况下，首选的分离机制（因此，粘合强度）将由拉伸强度最弱的粘合决定。因为拉伸强度由解束缚能的梯度决定，所以临界脱离力将由键能和有效键长两者决定。
The strength of receptor-mediated cell adhesion is directly controlled by the mechanism of cohesive failure between the cell surface and underlying substrate. Unbinding can occur either at the locus of the specific bond or within the bilayer, which results in tearing the hydrophobic anchors from the membrane interior. In this work, the surface force apparatus has been used to investigate the relationship between the receptor-ligand bond affinities and the dominant mechanism of receptor-coupled membrane detachment. The receptors and ligands used in this study were membrane-bound streptavidin and biotin analogs; respectively,with solution affinities ranging over 10 orders of magnitude. With the optical technique of the surface force apparatus, the occurrence of membrane rupture was directly visualized in situ. The latter observations together with measurements of the corresponding intermembrane adhesive strengths were used to identify the dominant failure pathway for each streptavidin-analog pair. Even in cases where the membrane pull-out energy exceeded the equilibrium bond energy, cohesive failure occurred within the membrane interior at nearly all bond affinities considered. These results are consistent with previous findings and provide direct support for the commonly held view that, under nonequilibrium conditions of applied external stress, the gradient of the bond energy, not the equilibrium bond energy alone, determines the adhesive strength. Furthermore, our findings directly demonstrate that, in the presence of competing failure mechanisms, the preferred detachment mechanism-hence, the adhesive strength-will be determined by the bond that exhibits the weakest tensile strength. Because the tensile strength is determined by the gradient of the unbinding energy, the critical detachment force will be determined by both the bond energy and the effective bond length.