Force history dependence of receptor-ligand dissociation.

Receptor-ligand bonds that mediate cell adhesion are often subjected to forces that regulate their dissociation via modulating off-rates. Off-rates control how long receptor-ligand bonds last and how much force they withstand. One should therefore be able to determine off-rates from either bond lifetime or unbinding force measurements. However, substantial discrepancies exist between the force dependence of off-rates derived from the two types of measurements even for the same interactions, e.g., selectins dissociating from their ligands, which mediate the tethering and rolling of leukocytes on vascular surfaces during inflammation and immune surveillance. We used atomic force microscopy to measure survival times of P-selectin dissociating from P-selectin glycoprotein ligand 1 or from an antibody in both bond lifetime and unbinding force experiments. By a new method of data analysis, we showed that the discrepancies resulted from the assumption that off-rates were functions of force only. The off-rates derived from forced dissociation data depended not only on force but also on the history of force application. This finding provides a new paradigm for understanding how force regulates receptor-ligand interactions.

[1]  M. U. Nollert,et al.  Tyrosine replacement in P-selectin glycoprotein ligand-1 affects distinct kinetic and mechanical properties of bonds with P- and L-selectin. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R. Alon,et al.  L-selectin Dimerization Enhances Tether Formation to Properly Spaced Ligand* , 2002, The Journal of Biological Chemistry.

[3]  K Schulten,et al.  Reconstructing potential energy functions from simulated force-induced unbinding processes. , 1997, Biophysical journal.

[4]  H. Flyvbjerg,et al.  Physics of bio-molecules and cells , 2002 .

[5]  Cheng Zhu,et al.  Distinct molecular and cellular contributions to stabilizing selectin-mediated rolling under flow , 2002, The Journal of cell biology.

[6]  J. Israelachvili,et al.  Polymer-cushioned bilayers. I. A structural study of various preparation methods using neutron reflectometry. , 1999, Biophysical journal.

[7]  Timothy A. Springer,et al.  The Kinetics of L-selectin Tethers and the Mechanics of Selectin-mediated Rolling , 1997, The Journal of cell biology.

[8]  Cheng Zhu,et al.  Direct observation of catch bonds involving cell-adhesion molecules , 2003, Nature.

[9]  M. U. Nollert,et al.  Dimerization of a selectin and its ligand stabilizes cell rolling and enhances tether strength in shear flow , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Cummings,et al.  The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine. , 1994, The Journal of biological chemistry.

[11]  J. Bechhoefer,et al.  Calibration of atomic‐force microscope tips , 1993 .

[12]  D. Hammer,et al.  Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow , 1995, Nature.

[13]  E. Evans.  Probing the relation between force--lifetime--and chemistry in single molecular bonds. , 2001, Annual review of biophysics and biomolecular structure.

[14]  V. Moy,et al.  Force spectroscopy of the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. , 2002, Biophysical journal.

[15]  R. McEver.  Selectins: lectins that initiate cell adhesion under flow. , 2002, Current opinion in cell biology.

[16]  T. Springer,et al.  The kinetics and shear threshold of transient and rolling interactions of L-selectin with its ligand on leukocytes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  O. McCarty,et al.  Single Molecule Characterization of P-selectin/Ligand Binding* 210 , 2003, The Journal of Biological Chemistry.

[18]  R. Waugh,et al.  A microcantilever device to assess the effect of force on the lifetime of selectin-carbohydrate bonds. , 2001, Biophysical journal.

[19]  R. Merkel,et al.  Energy landscapes of receptor–ligand bonds explored with dynamic force spectroscopy , 1999, Nature.

[20]  V. Moy,et al.  Molecular basis of the dynamic strength of the sialyl Lewis X--selectin interaction. , 2004, Chemphyschem : a European journal of chemical physics and physical chemistry.

[21]  K. Schulten,et al.  Molecular dynamics study of unbinding of the avidin-biotin complex. , 1997, Biophysical journal.

[22]  Evan Evans,et al.  Dynamic Force Spectroscopy , 2002 .

[23]  H. Güntherodt,et al.  Dynamic force spectroscopy of single DNA molecules. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Weis,et al.  Supported planar membranes in studies of cell-cell recognition in the immune system. , 1986, Biochimica et biophysica acta.

[25]  D. Vestweber,et al.  Mechanisms that regulate the function of the selectins and their ligands. , 1999, Physiological reviews.

[26]  Harold P. Erickson,et al.  Force Measurements of the α5β1 Integrin–Fibronectin Interaction , 2003 .

[27]  S. Redick,et al.  Force Measurements of the a 5 b 1 Integrin-Fibronectin Interaction , 2003 .

[28]  G. I. Bell.  Models for the specific adhesion of cells to cells. , 1978, Science.

[29]  J. Fritz,et al.  Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  E. Evans,et al.  Dynamic strength of molecular adhesion bonds. , 1997, Biophysical journal.

[31]  P Kolb,et al.  Energy landscape of streptavidin-biotin complexes measured by atomic force microscopy. , 2000, Biochemistry.

[32]  K. Konstantopoulos,et al.  Distinct kinetic and mechanical properties govern selectin-leukocyte interactions , 2004, Journal of Cell Science.

[33]  D. Torney,et al.  The reaction-limited kinetics of membrane-to-surface adhesion and detachment , 1988, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[34]  Cheng Zhu,et al.  Low Force Decelerates L-selectin Dissociation from P-selectin Glycoprotein Ligand-1 and Endoglycan* , 2004, Journal of Biological Chemistry.

[35]  E L Berg,et al.  A direct comparison of selectin-mediated transient, adhesive events using high temporal resolution. , 1999, Biophysical journal.

[36]  R P McEver,et al.  Adhesive Interactions of Leukocytes, Platelets, and the Vessel Wall during Hemostasis and Inflammation , 2001, Thrombosis and Haemostasis.

[37]  Cheng Zhu,et al.  Mechanical switching and coupling between two dissociation pathways in a P-selectin adhesion bond. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[38]  T. Springer,et al.  Selectin receptor-ligand bonds: Formation limited by shear rate and dissociation governed by the Bell model. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Zhu,et al.  Kinetics and mechanics of cell adhesion. , 2000, Journal of biomechanics.

[40]  P. Bongrand,et al.  Measuring Receptor/Ligand Interaction at the Single-Bond Level: Experimental and Interpretative Issues , 2002, Annals of Biomedical Engineering.

[41]  Gerhard Hummer,et al.  Kinetics from nonequilibrium single-molecule pulling experiments. , 2003, Biophysical journal.

[42]  Cheng Zhu,et al.  Catch bonds govern adhesion through L-selectin at threshold shear , 2004, The Journal of cell biology.

[43]  M. Hegner,et al.  Model energy landscapes and the force-induced dissociation of ligand-receptor bonds. , 2000, Biophysical Journal.

[44]  R. Cummings,et al.  P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin , 1995, The Journal of cell biology.

[45]  R. Alon,et al.  Cytoplasmic anchorage of L-selectin controls leukocyte capture and rolling by increasing the mechanical stability of the selectin tether , 2001, The Journal of cell biology.

[46]  Rodger P. McEver,et al.  Rapid neutrophil adhesion to activated endothelium mediated by GMP-140 , 1990, Nature.

[47]  Evan Evans,et al.  Chemically distinct transition states govern rapid dissociation of single L-selectin bonds under force , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[48]  R. Merkel,et al.  STATISTICAL BREAKAGE OF SINGLE PROTEIN A-IGG BONDS REVEALS CROSSOVER FROM SPONTANEOUS TO FORCE-INDUCED BOND DISSOCIATION , 1999 .

[49]  Ariel Solomon,et al.  Avidity enhancement of L-selectin bonds by flow , 2003, The Journal of cell biology.