Modeling Mechanisms of Cell Secretion
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Modeling Mechanisms of Cell Secretion Krasimira Tsaneva-Atanasova • Hinke M. Osinga Joe¨l Tabak • Morten Gram Pedersen
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Received: 7 June 2010 / Accepted: 5 July 2010 / Published online: 27 July 2010 Ó Springer Science+Business Media B.V. 2010
Abstract Secretion is a fundamental cellular process involving the regulated release of intracellular products from cells. Physiological functions such as neurotransmission, or the release of hormones and digestive enzymes, are all governed by cell secretion. Anomalies in the processes involved in secretion contribute to the development and progression of diseases such as diabetes and other hormonal disorders. To unravel the mechanisms that govern such diseases, it is essential to understand how hormones, growth factors and neurotransmitters are synthesized and processed, and how their signals are recognized, amplified and transmitted by intracellular signaling pathways in the target cells. Here, we discuss diverse aspects of the detailed mechanisms involved in secretion based on mathematical models. The models range from stochastic ones describing the trafficking of secretory vesicles to deterministic ones investigating the regulation of cellular processes that underlie hormonal secretion. In all cases, the models are closely related to experimental results and suggest theoretical predictions for the secretion mechanisms. Keywords Mathematical model Vesicles Bifurcation analysis Exocytosis Hormone secretion K. Tsaneva-Atanasova (&) H. M. Osinga Bristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Queen’s Building, University Walk, Bristol BS8 1TR, UK e-mail: [email protected] H. M. Osinga e-mail: [email protected] J. Tabak Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA e-mail: [email protected] M. G. Pedersen Department of Information Engineering, University of Padua, 35131 Padua, Italy e-mail: [email protected]
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1 Introduction Hormone secretion is a complex process, which involves the packaging of the hormone in secretory vesicles, transportation to the cell membrane and calciumtriggered exocytosis. The level of detail at which each of these steps is represented in mathematical models varies greatly. The goal is the development of multi-scale models that integrate aspects at the molecular, cell, and organ levels. Although it is very challenging to obtain such multi-scale models, they would allow for simulation and other numerical techniques to analyze important inference and prediction tasks, such as early warning and optimization of resources, for better treatment of hormonal disorders. An important goal in cell biology is to understand how physiological function is translated into signaling or secretion processes and vice-versa. We have selected different aspects of the mechanisms involved in secretion and focus on the development of mathematical models that can inform experiments and help to unde
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