Thu, 24 Jul 2008 19:34:15 BST CiteULike: matthewhflamm strength http://www.citeulike.org/user/matthewhflamm/tag/strength CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/matthewhflamm/article/2599294 <i>Proceedings of the National Academy of Sciences, Vol. 99, No. 11. (28 May 2002), pp. 7426-7431.</i><br /><br />Integrin activation states determine the ability of these receptors to mediate cell-matrix and cell-cell interactions. The prototypic example of this phenomenon is the platelet integrin, [alpha]IIb[beta]3. In unstimulated platelets, [alpha]IIb[beta]3 is inactive, whereas exposing platelets to an agonist such as ADP or thrombin enables [alpha]IIb[beta]3 to bind ligands such as fibrinogen and von Willebrand factor. To study the regulation of integrin activation states at the level of single molecules, we developed a model system based on laser tweezers, enabling us to determine the rupture forces required to separate single ligand-receptor pairs by using either purified proteins or intact living cells. Here, we show that rupture forces of individual fibrinogen molecules and either purified [alpha]IIb[beta]3 or [alpha]IIb[beta]3 on the surface of living platelets were 60 to 150 pN with a peak yield strength of 80-100 pN. Platelet stimulation using either ADP or the thrombin receptor-activating peptide enhanced the accessibility but not the adhesion strength of single [alpha]IIb[beta]3 molecules, indicating that there are only two states of [alpha]IIb[beta]3 activation. Thus, we found it possible to use laser tweezers to measure the regulation of forces between individual ligand-receptor pairs on living cells. This methodology can be applied to the study of other regulated cell membrane receptors using the ligand-receptor yield strength as a direct measure of receptor activation/inactivation state. 10.1073/pnas.112194999 Binding strength and activation state of single fibrinogen-integrin pairs on living cells Rustem Litvinov Henry Shuman Joel Bennett John Weisel doi:10.1073/pnas.112194999 Proceedings of the National Academy of Sciences, Vol. 99, No. 11. (28 May 2002), pp. 7426-7431. 2008-03-26T17:51:03-00:00 2002 Proceedings of the National Academy of Sciences 99 11 7426 7431 fibrinogen strength