Document Detail

Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow.
MedLine Citation:
PMID:  15574709     Owner:  NLM     Status:  MEDLINE    
Transient capture of cells or model microspheres from flow over substrates sparsely coated with adhesive ligands has provided significant insight into the unbinding kinetics of leukocyte:endothelium adhesion complexes under external force. Whenever a cell is stopped by a point attachment, the full hydrodynamic load is applied to the adhesion site within an exceptionally short time-less than the reciprocal of the hydrodynamic shear rate (e.g., typically <0.01 s). The decay in numbers of cells or beads that remain attached to a surface has been used as a measure of the kinetics of molecular bond dissociation under constant force, revealing a modest increase in detachment rate at growing applied shear stresses. On the other hand, when detached under steady ramps of force with mechanical probes (e.g., the atomic force microscope and biomembrane force probe), P-selectin:PSGL-1 adhesion bonds break at rates that increase enormously under rising force, yielding 100-fold faster off rates at force levels comparable to high shear. The comparatively weak effect of force on tether survival in flow chamber experiments could be explained by a possible partition of the load amongst several bonds. However, a comprehensive understanding of the difference in kinetic behavior requires us to also inspect other factors affecting the dynamics of attachment-force buildup, such as the interfacial compliance of all linkages supporting the adhesion complex. Here, combining the mechanical properties of the leukocyte interface measured in probe tests with single-bond kinetics and the kinetics of cytoskeletal dissociation, we show that for the leukocyte adhesion complex P-selectin:PSGL-1, a detailed adhesive dynamics simulation accurately reproduces the tethering behavior of cells observed in flow chambers. Surprisingly, a mixture of 10% single bonds and 90% dimeric bonds is sufficient to fully match the data of the P-selectin:PSGL-1 experiments, with the calculated decay in fraction of attached cells still appearing exponential.
Michael R King; Volkmar Heinrich; Evan Evans; Daniel A Hammer
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Validation Studies     Date:  2004-12-01
Journal Detail:
Title:  Biophysical journal     Volume:  88     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-01     Completed Date:  2005-07-06     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1676-83     Citation Subset:  IM    
Department of Biomedical Engineering, University of Rochester, Rochester, New York 14642, USA.
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MeSH Terms
Binding Sites
Blood Flow Velocity / physiology*
Cell Adhesion / physiology
Computer Simulation
Cytoskeleton / physiology*
Leukocytes / physiology*,  ultrastructure
Models, Cardiovascular*
Nanotechnology / methods
P-Selectin / metabolism*
Protein Binding
Shear Strength
Grant Support
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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