Resumen de Mathematical models and multiscale simulations of cellular secretion processes
Virginia González Vélez
Exocytosis is the cellular process whereby a product such as a hormone or a neurotransmitter is released as a response to stimulation. There are a lot of exocytotic cells in mammals, and each cell type has their specific subcellular mechanisms, needed to achieve the final substance release. Therefore, unveiling the role of subcellular mechanisms in secretion processes is highly relevant to understand disease evolution and possible therapies. The efficiency of the coupling between stimulus and secretion is mainly managed by an intracellular Ca2+ signal. In the present thesis, a modeling approach of Ca2+-triggered secretion is presented for some different cellular types. In particular, cells with different characteristic time scales were chosen in order to discuss about a multiscale approach for studying spatiotemporal features of secretion processes. The object of this piece of research ranges from a short temporal scale (fast secretion) up to a long temporal scale (slow secretion). The study also discuss the intermediate temporal scale, and the joining point between theoretical methodologies. Cellular Ca2+ and secretion dynamics have been studied in the abovementioned timescales for the calyx of Held presynaptic terminal, the pancreatic alpha cell, and the adrenal chromaffin cell, respectively. The aim of this work has been twofold: first, to develop mathematical models that follow actual sub-cellular mechanisms involved in secretion, and second, to make simulations on these models in order to reproduce the experimentally observed Ca2+ and secretory behaviour. The ultimate goal is to propose common methodologies and algorithms to support the theoretical approach for studying multiscale cellular processes.
