Jose Manuel Garcia-Aznar

arXiv2025

A Data-Enhanced Agent-Based Model for Simulating 3D Cancer Spheroid Growth: Integrating Metabolism and Mechanics

Cancer research has shifted from a purely gene-centric view to a more holistic understanding that recognizes the critical role of the tumour microenvironment, where mechanics and metabolism are key drivers of disease progression. However, the intricate interplay between these multifactorial mechanisms remains poorly understood. To address this gap, we present an agent-based computational model (ABM) that integrates tumour metabolism and mechanics to study 3D cancer spheroid growth. Our approach unifies the metabolism and mechanical aspects of tumour development within an integral model for cancer spheroid formation and growth. In addition to that, we performed a computational calibration of the parameters and tested the model versatility to reproduce different cellular behaviours. Our model reproduced qualitatively and quantitatively the experimental results of spheroid growth obtained in the lab and also allowed to discern different dynamics that cancer cells can present under the same conditions, providing insight into the potential factors contributing to the variability in the size of spheroids. Furthermore, it also showed its adaptability to reproduce diferent cell lines and behaviours by tuning its parameters. This study highlights the significant potential and versatility of integrative modelling approaches in the field of cancer research, not only as a tool to complement in vitro studies, but also as independent tools to derive conclusions from the physical reality.

cs.CE↗

arXiv2018

Balance of Mechanical Forces Drives Endothelial Gap Formation and May Facilitate Cancer and Immune-Cell Extravasation

The formation of gaps in the endothelium is a crucial process underlying both cancer and immune cell extravasation, contributing to the functioning of the immune system during infection, the unfavorable development of chronic inflammation and tumor metastasis. Here, we present a stochastic-mechanical multiscale model of an endothelial cell monolayer and show that the dynamic nature of the endothelium leads to spontaneous gap formation, even without intervention from the transmigrating cells. These gaps preferentially appear at the vertices between three endothelial cells, as opposed to the border between two cells. We quantify the frequency and lifetime of these gaps, and validate our predictions experimentally. Interestingly, we find experimentally that cancer cells also preferentially extravasate at vertices, even when they first arrest on borders. This suggests that extravasating cells, rather than initially signaling to the endothelium, might exploit the autonomously forming gaps in the endothelium to initiate transmigration.

q-bio.CB↗