Stochastic models of receptor oligomerization by bivalent ligand.
In this paper, we develop stochastic models of receptor binding by a bivalent ligand. A detailed kinetic study allows us to analyse the role of cross-linking in cell activation by receptor oligomerization. We show how oligomer formation could act to buffer intracellular signalling against stochastic fluctuations. In addition, we put forward the hypothesis that formation of long linear oligomers increases the range of ligand concentration to which the cell is responsive, whereas formation of closed oligomers increases ligand concentration specificity. Thus, different physiological functions requiring different degrees of specificity to ligand concentration would favour formation of oligomers with different lengths and geometries. Furthermore, provided that ligand concentration specificity is taken as a design principle, our model enables us to estimate parameters, such as the minimum proportion of receptors, that must engage in oligomer formation in order to trigger a cellular response.
Alarcón
Tomás
T
Bioinformatics Unit, Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK. t.alarcon@cs.ucl.ac.uk
Page
Karen M
KM
D003198:Computer Simulation; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D009010:Monte Carlo Method; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013269:Stochastic Processes; D013379:Substrate Specificity
D008024:Ligands; D011971:Receptors, Immunologic