Document Detail


Stochastic simulation of hemagglutinin-mediated fusion pore formation.
MedLine Citation:
PMID:  11509351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies on fusion between cell pairs have provided evidence that opening and subsequent dilation of a fusion pore are stochastic events. Therefore, adequate modeling of fusion pore formation requires a stochastic approach. Here we present stochastic simulations of hemagglutinin (HA)-mediated fusion pore formation between HA-expressing cells and erythrocytes based on numerical solutions of a master equation. The following elementary processes are taken into account: 1) lateral diffusion of HA-trimers and receptors, 2) aggregation of HA-trimers to immobilized clusters, 3) reversible formation of HA-receptor contacts, and 4) irreversible conversion of HA-receptor contacts into stable links between HA and the target membrane. The contact sites between fusing cells are modeled as superimposed square lattices. The model simulates well the statistical distribution of time delays measured for the various intermediates of fusion pore formation between cell-cell fusion complexes. In particular, these are the formation of small ion-permissive and subsequent lipid-permissive fusion pores detected experimentally (R. Blumenthal, D. P. Sarkar, S. Durell, D. E. Howard, and S. J., J. Cell Biol. 135:63-71). Moreover, by averaging the simulated individual stochastic time courses across a larger population of cell-cell-complexes the model also provides a reasonable description of kinetic measurements on lipid mixing in cell suspensions (T. Danieli, S. L. Pelletier, Y.I. Henis, and J. M. White, 1996, J. Cell Biol. 133:559-569).
Authors:
S Schreiber; K Ludwig; A Herrmann; H G Holzhütter
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biophysical journal     Volume:  81     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-17     Completed Date:  2001-10-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1360-72     Citation Subset:  IM    
Affiliation:
Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie/Biophysik, D-10115 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cell Fusion*
Cell Membrane / chemistry,  metabolism*
Computer Simulation*
Hemagglutinins / chemistry,  metabolism*
Intercellular Junctions / chemistry,  metabolism*
Kinetics
Markov Chains
Models, Biological
Receptors, Cell Surface / metabolism*
Reproducibility of Results
Stochastic Processes
Chemical
Reg. No./Substance:
0/Hemagglutinins; 0/Receptors, Cell Surface
Comments/Corrections

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