Noise from spatial heterogeneity changes signal amplification magnitude and increases the variability in dose responses

Kim, J., Mao, X. and Heslop-Harrison, P. (2008) Noise from spatial heterogeneity changes signal amplification magnitude and increases the variability in dose responses. In: The 9th International Conference on Systems Biology, Goethenburg, Sweden, 23-27 Aug 2008,

Abstract

In most molecular level simulations, spatial heterogeneity is neglected by the well-mixed condition assumption. However, the signals of biomolecular networks are affected from both time and space, which are responsible for diverse physiological responses. To account the spatial heterogeneity in the kinetic model, we consider multiple subvolumes of a reaction, introduce parameters representing transfer of ligands between the volumes, and reduce this to an error-term representing the difference between the well-mixed condition and the actual spatial factors. The error-term approach allows modelling of varying spatial heterogeneity without increasing computational burden exponentially. The effect of varying this term, d, between 0 (well-mixed) and 1 (no mixing) and of adding noise to the kinetic constants was then investigated and correlated with knowledge of the behaviour of real systems and situations where network models are inadequate. The spatial distribution effects on the epidermal growth factor receptor (EGFR) in human mammary epithelial tissue, which is involved in proliferation and tumorigenesis, are studied by introducing noisy kinetic constants. The steady-state of the dose response in the EGFR is strongly affected by spatial fluctuations. The ligand-bound receptor is reduced up to 50% from the response without spatial fluctuations and the variance of the steady-state is increased at least 2-fold from the one for no spatial fluctuations. On the other hand, dynamic properties such as the rising time and overshoot are less sensitive to spatial noise.

• Item Type: Conference Proceedings
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kim, Dr Jongrae
• Authors: Kim, J., Mao, X., and Heslop-Harrison, P.
• Subjects: Q Science > Q Science (General); Q Science > QH Natural history > QH301 Biology
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering; College of Science and Engineering > School of Engineering > Autonomous Systems and Connectivity
• Copyright Holders: Copyright © 2008 The Author
• First Published: First published in Proceedings of the 9th International Conference on Systems Biology
• Publisher Policy: Reproduced with permission of the author.