Ligand Rebinding: Self-consistent Mean-field Theory and Numerical Simulations Applied to SPR Studies

作者: Kimberly Forsten-Williams , Uwe C. Tauber , Manoj Gopalakrishnan , Thomas E. Ryan , Luz Padro

DOI:

关键词:

摘要: Rebinding of dissociated ligands from cell surface proteins can confound quantitative measurements dissociation rates important for characterizing the affinity binding interactions. This be true also in vitro techniques such as plasmon resonance (SPR). We present experimental results using SPR interaction insulin-like growth factor-I (IGF-I) with one its proteins, IGF protein-3 (IGFBP-3), and show that rebinding, even addition soluble heparin phase, does not exhibit expected exponential decay characteristic a 1:1 reaction. thus consider effect (multiple) rebinding events and, within self-consistent mean-field approximation, we derive complete mathematical form fraction bound ligand function time. that, except very low coverage/association rate, this is non-exponential at all times, indicating multiple strongly influence early times. compare numerical simulations find good agreement, although deviations are measurable certain cases. Our analysis IGF-I-IGFBP-3 data indicates prominent system theoretical predictions fit well. provide means analyzing biosensor where problematic methodology to do so presented.

参考文章(34)
T. A. A. B., A. Erdelyi, Tables of Integral Transforms. I The Mathematical Gazette. ,vol. 39, pp. 337- ,(1955) , 10.2307/3608613
Man-Sau Wong, Chi-Chun Fong, Mengsu Yang, Biosensor measurement of the interaction kinetics between insulin-like growth factors and their binding proteins. Biochimica et Biophysica Acta. ,vol. 1432, pp. 293- 301 ,(1999) , 10.1016/S0167-4838(99)00106-5
David A. Edwards, Byron Goldstein, Donald S. Cohen, Transport effects on surface-volume biological reactions. Journal of Mathematical Biology. ,vol. 39, pp. 533- 561 ,(1999) , 10.1007/S002850050177
C. DeLisi, F. W. Wiegel, Effect of nonspecific forces and finite receptor number on rate constants of ligand--cell bound-receptor interactions Proceedings of the National Academy of Sciences of the United States of America. ,vol. 78, pp. 5569- 5572 ,(1981) , 10.1073/PNAS.78.9.5569
David G Myszka, Thomas A Morton, CLAMP©: a biosensor kinetic data analysis program Trends in Biochemical Sciences. ,vol. 23, pp. 149- 150 ,(1998) , 10.1016/S0968-0004(98)01183-9
Noam Agmon, Diffusion with back reaction Journal of Chemical Physics. ,vol. 81, pp. 2811- 2817 ,(1984) , 10.1063/1.447954
David G. Myszka, Improving biosensor analysis. Journal of Molecular Recognition. ,vol. 12, pp. 279- 284 ,(1999) , 10.1002/(SICI)1099-1352(199909/10)12:5<279::AID-JMR473>3.0.CO;2-3