help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Biophys. J. BioFAST: First Published April 7, 2006. doi:10.1529/biophysj.106.082909
© 2006 by the Biophysical Society.

A more recent version of this article appeared on July 1, 2006.
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
biophysj.106.082909v1
91/1/352    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Long, M.
Right arrow Articles by Zhu, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Long, M.
Right arrow Articles by Zhu, C.

CELL BIOPHYSICS

PROBABILISTIC MODELING OF ROSETTE FORMATION

Mian Long 1*, Juan Chen 1, Ning Jiang 2, Periasamy Selvaraj 3, Rodger P. McEver 4 and Cheng Zhu 2

1 Institute of Mechanics, Chinese Academy of Sciences
2 Georgia Institute of Technology
3 Emory University School of Medicine
4 Oklahoma Medical Research Foundation

* To whom correspondence should be addressed. E-mail: mlong{at}imech.ac.cn.

Submitted on February 8, 2006
Revised on March 15, 2006
Accepted on 17 March 2006


  Abstract
Rosetting, or forming a cell aggregate between a single target nucleated cell and a number of red blood cells (RBCs), is a simple assay for cell adhesion mediated by specific receptor-ligand interaction. For example, rosette formation between sheep RBC and human lymphocytes has been used to differentiate T cells from B cells. Rosetting assay is commonly used to determine the interaction of Fc gamma receptors (Fc{gamma}R) expressed on inflammatory cells and IgG coated on RBCs. Despite its wide use in measuring cell adhesion, the biophysical parameters of rosette formation have not been well characterized. Here we developed a probabilistic model to describe the distribution of rosette sizes, which is Poissonian. The average rosette size is predicted to be proportional to the apparent two-dimensional (2D) binding affinity of the interacting receptor-ligand pair and their site densities. The model has been supported by experiments of rosettes mediated by four molecular interactions: Fc{gamma}RIII interacting with IgG, T cell receptor and co-receptor CD8 interacting with antigen peptide presented by major histocompatibility molecule, P-selectin interacting with P-selectin glycoprotein ligand 1 (PSGL-1), and L-selectin interacting with PSGL-1. The latter two are structurally similar and different from the former two. Fitting the model to data enabled us to evaluate the apparent effective 2D binding affinity of the interacting molecular pairs: 7.19 x 10-5 µm4 for Fc{gamma}RIII-IgG interaction, 4.66 x 10-3 µm4 for P-selectin-PSGL-1 interaction, and 0.94 x 10-3 µm4 for L-selectin-PSGL-1 interaction. These results elucidate the biophysical mechanism of rosette formation and enable it to become a semi-quantitative assay that relates the rosette size to the effective affinity for receptor-ligand binding.

Key Words: Poisson distribution, binding affinity, probabilistic model, rosette size






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by the Biophysical Society.