Differential segregation in a cell-cell contact interface: the dynamics of the immunological synapse
Burroughs, Nigel John and Wülfing, Christoph. (2002) Differential segregation in a cell-cell contact interface: the dynamics of the immunological synapse. Biophysical Journal, Vol.83 (No.4). pp. 1784-1796. ISSN 0006-3495
WRAP_Burroughs_Differentail_segregation.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://dx.doi.org/10.1016/S0006-3495(02)73944-1
Receptor-ligand couples in the cell-cell contact interface between a T cell and an antigen-presenting cell form distinct geometric patterns and undergo spatial rearrangement within the contact interface. Spatial segregation of the antigen and adhesion receptors occurs within seconds of contact, central aggregation of the antigen receptor then occurring over 1-5 min. This structure, called the immunological synapse, is becoming a paradigm for localized signaling. However, the mechanisms driving its formation, in particular spatial segregation, are currently not understood. With a reaction diffusion model incorporating thermodynamics, elasticity, and reaction kinetics, we examine the hypothesis that differing bond lengths (extracellular domain size) is the driving force behind molecular segregation. We derive two key conditions necessary for segregation: a thermodynamic criterion on the effective bond elasticity and a requirement for the seeding/nucleation of domains. Domains have a minimum length scale and will only spontaneously coalesce/aggregate if the contact area is small or the membrane relaxation distance large. Otherwise, differential attachment of receptors to the cytoskeleton is required for central aggregation. Our analysis indicates that differential bond lengths have a significant effect on synapse dynamics, i.e., there is a significant contribution to the free energy of the interaction, suggesting that segregation by differential bond length is important in cell-cell contact interfaces and the immunological synapse.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RB Pathology|
|Divisions:||Faculty of Science > Mathematics|
|Library of Congress Subject Headings (LCSH):||T cells -- Mathematical models, Atomic force microscopy, Immune recognition, Lipids -- Research, Lymphocytes -- Receptors|
|Journal or Publication Title:||Biophysical Journal|
|Official Date:||October 2002|
|Page Range:||pp. 1784-1796|
|Access rights to Published version:||Open Access|
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