The Influence of Nutrients Diffusion on a Metabolism-driven Model of a Multi-cellular System

Issue title: Interdisciplinary Nature of Information Processing Special Issue Dedicated to Giancarlo Mauri on the Occasion of His 70th Birthday

Guest editors: Alberto Dennunzio, Gheorghe Păun, Grzegorz Rozenberg and Claudio Zandron

Article type: Research Article

Authors: Maspero, Davide^{a; *} | Damiani, Chiara^{a; †} | Antoniotti, Marco^{a; ‡} | Graudenzi, Alex^{a; §} | Di Filippo, Marzia^b | Vanoni, Marco^{b; £} | Caravagna, Giulio^c | Colombo, Riccardo^d | Ramazzotti, Daniele^e | Pescini, Dario^{f; C}

Affiliations: [a] Department of Informatics Systems and Communication, Univ. of Milano-Bicocca, Milan, Italy | [b] Department of Biotechnology and Biosciences, Univ. Milano-Bicocca, Milan, Italy | [c] Data Scientist, Institute of Cancer Research, ICR, London, UK | [d] Department of Biomedical and Clinical Sciences “L. Sacco”, Univ. of Milan, Milan, Italy | [e] Department of Pathology, Stanford University, Stanford, CA 94305, USA | [f] Department of Statistics and Quantitative Methods, Univ. of Milano-Bicocca, Milan, Italy. [email protected]

Correspondence: [C] Address for correspondence: Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Via Bicocca degli Arcimboldi, 8 - 20126 Milan.

Note: [*] Also affiliated at: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Note: [†] Also affiliated at: SYSBIO Centre of Systems Biology, Univ. of Milano-Bicocca, Milan, Italy

Note: [‡] Also affiliated at: NeuroMI Milan Center for Neuroscience, Univ. of Milano-Bicocca, Milan, Italy

Note: [§] Also affiliated at: Institute of Molecular Bioimaging and Physiology, Italian National Research Council, Milan, Italy.

Note: [£] Also affiliated at: SYSBIO Centre of Systems Biology, Univ. of Milano-Bicocca, Milan, Italy.

Abstract: The metabolic processes related to the synthesis of the molecules needed for a new round of cell division underlie the complex behaviour of cell populations in multi-cellular systems, such as tissues and organs, whereas their deregulation can lead to pathological states, such as cancer. Even within genetically homogeneous populations, complex dynamics, such as population oscillations or the emergence of specific metabolic and/or proliferative patterns, may arise, and this aspect is highly amplified in systems characterized by extreme heterogeneity. To investigate the conditions and mechanisms that link metabolic processes to cell population dynamics, we here employ a previously introduced multi-scale model of multi-cellular system, named FBCA (Flux Balance Analysis with Cellular Automata), which couples biomass accumulation, simulated via Flux Balance Analysis of a metabolic network, with the simulation of population and spatial dynamics via Cellular Potts Models. In this work, we investigate the influence that different modes of nutrients diffusion within the system may have on the emerging behaviour of cell populations. In our model, metabolic communication among cells is allowed by letting secreted metabolites to diffuse over the lattice, in addition to diffusion of nutrients from given sources. The inclusion of the diffusion processes in the model proved its effectiveness in characterizing plausible biological scenarios.

Keywords: Multi-scale modeling, Cellular Potts Model, Flux Balance Analysis, Diffusion, Cancer development

DOI: 10.3233/FI-2020-1883

Journal: Fundamenta Informaticae, vol. 171, no. 1-4, pp. 279-295, 2020