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Event tracking model of adhesion identifies load‐bearing bonds in leukocyte rolling at low shear
Author(s) -
Pospieszalska Maria K.,
Zarbock Alexander,
Pickard John E.,
Ley Klaus
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.166.6
Subject(s) - bond , shear stress , bearing (navigation) , shear (geology) , adhesion , load bearing , mechanics , dissociation (chemistry) , materials science , chemistry , structural engineering , biophysics , physics , computer science , engineering , composite material , biology , artificial intelligence , finance , economics
P‐selectin binding to PSGL‐1 mediates leukocyte rolling under conditions of inflammation and injury. Here, we develop a three‐dimensional, direct, stochastic π‐calculus‐driven Event Tracking Model of Adhesion (ETMA) to capture the dynamics of and make predictions about P‐selectin—PSGL‐1 bonds under low shear stress conditions. Instantaneous displacements, translational and rotational velocities, leukocyte‐endothelium distances, and number, location and lifetime of total and load‐bearing bonds are derived from measured physiological and biophysical parameters of leukocyte rolling and molecular bond properties. The model explains the commonly observed “stop‐start” type rolling behavior, and reveals that a few load‐bearing bonds are sufficient to support rolling while overall a large number of bonds dissociate before becoming load‐bearing. The model provides high resolution data corresponding well with experimental results obtained by our own and other groups. ETMA is the first model that reconstructs the exact sequence of bond formation and dissociation events in the rolling process and is uniquely able to identify the behavior of load‐bearing bonds. This work was supported in part by the NIH (grant 2R01EB002185) and Deutsche Forschungsgemeinschaft (grant AZ 428/2‐1).