Different computational-based approaches have been extensively used for simulating the morphogenesis of multicellular systems. On the one hand, continuum-based models allow the simulation of large cell populations at the macroscopic level. This is the case for reaction-diffusion systems based on partial differential equations (PDEs) or positional information (PI). On the other hand, discrete approaches with agent-based models considering cells as autonomous entities that interact among themselves and with the microenvironment. These models have been widely employed, for instance, to simulate tumor growth in vitro [1], to study the role of extracellular matrix density in cell migration within solid tumor spheroids [2] or lumen-based organoids [3], collective cell migration [4].
In this work, we present the results of different in-vitro experiments corresponding to the morphogenesis of different human-cell-based tumor organoids, from neuroblastoma, pancreas and lung. Normally, all these experiments follow a similar protocol [5], where individual tumor cells are cultured in 3D microfluidic devices upon collagen-type I hydrogels. With the time these tumor cells are able to proliferate, self-organizing according to the architecture of the hydrogel, creating different structures. The evolution of size and shape of these tumor structures are quantified by means of microscopy-based images. Thus, this kind of organ-on-a-chip experiments constitutes a novel modelling strategy of in vitro multicellular human systems that in combination with numerical simulations provide a relevant tool for research in mechanobiology.
Therefore, in this presentation I will show our engineering-based strategy in which we integrate computational models and in-vitro experiments in order to tackle of how matrix mechanics is regulating the size and organization of tumour organoids. Different computer-based modelling strategies will be presented to simulate the morphogenesis of these in-vitro tumor organoids, clearly identifying the challenges that we face in these numerical simulations, mainly associated to the variability observed in the experiments and the difficulties associated to the parameters calibration process.
References:
[1] Hervas-Raluy, S., Wirthl, B., ... & Wall, W. A. (2023). Tumour growth: An approach to calibrate parameters of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment. Computers in Biology and Medicine.
[2] Gonçalves, I. G., & Garcia-Aznar, J. M. (2021). Extracellular matrix density regulates the formation of tumour spheroids through cell migration. PLoS computational biology, 17(2), e1008764.
[3] Camacho-Gómez, D., García-Aznar, J. M., & Gómez-Benito, M. J. (2022). A 3D multi-agent-based model for lumen morphogenesis: the role of the biophysical properties of the extracellular matrix. Engineering with Computers, 38(5), 4135-4149.
[4] González-Valverde, I., & García-Aznar, J. M. (2018). Mechanical modeling of collective cell migration: An agent-based and continuum material approach. Computer Methods in Applied Mechanics and Engineering, 337, 246-262.
[5] Plou, J., Juste-Lanas, Y., Olivares, V., Del Amo, C., Borau, C., & García-Aznar, J. M. (2018). From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-β. Scientific reports, 8(1), 12723.
Acknowledgments: This work was supported by the European Research Council (ICoMICS Adv grant: 101018587 and the Spanish Ministry of Science and Innovation (PID2021-122409OB-C21).
