Receptor-cytoskeletal unbinding in detachment of P-selectin from PSGL-1 on leukocytes

E. Evans, V. Heinrich, A. Leung

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Using a biomembrane force probe decorated with P-selectin, discrete bonds were formed to PSGL-1 receptors on PMN surfaces and detached at speeds from ∼ 1 - 100 μm/sec. High resolution tracking of the distance between probe tip and PMN revealed an initial elastic deformation that was either terminated by abrupt detachment or interrupted by yield and fluid-like extrusion of a macroscale tether plus subsequent detachment. Selecting tests that exhibited first yield then a single detachment step, we were able to quantify cohesive strengths between single PSGL-1 receptors and the PMN cytoskeleton. Prior to yield, the constant force rate was set by elastic stiffness (∼ 0.25 pN/nm) of the cytostructure and the pulling speed. Collected at rates over a span from 265 pN/sec to 38000 pN/sec, distributions of yield forces were found to agree precisely with probability densities for rupture of a single bond defined by a spontaneous dissociation rate of ∼ 0.5/sec and an energy barrier projected at ∼ 0.25 nm along the direction of force. By comparison, single P-selectin bonds to PSGL-1 covalently attached to microspheres were slightly stronger at all loading rates as characterized by a spontaneous dissociation rate of ∼ 0.15/sec and an energy barrier projected at ∼ 0.22 nm. Weaker anchoring to the cytoskeleton implies frequent tether formation that can reduce the hydrodynamic load applied to selectin bonds and prolong PMN attachments to vessel walls under conditions of flow.

Original languageEnglish (US)
Title of host publicationAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Pages580-581
Number of pages2
Volume1
StatePublished - 2002
Externally publishedYes
EventProceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS) - Houston, TX, United States
Duration: Oct 23 2002Oct 26 2002

Other

OtherProceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS)
CountryUnited States
CityHouston, TX
Period10/23/0210/26/02

ASJC Scopus subject areas

  • Bioengineering

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    Evans, E., Heinrich, V., & Leung, A. (2002). Receptor-cytoskeletal unbinding in detachment of P-selectin from PSGL-1 on leukocytes. In Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings (Vol. 1, pp. 580-581)