Modelling Tumoroid Collective Migration: Interplay of Pair Active Brownian Motion and the ExtraCellular Matrix

Understanding the collective migration in tumoroids, in-vitro tumour spheroids, provides insights into breast cancer metastasis. Recent observations by Schmidt et al. have revealed their intriguing mechanical and morphological properties. Here, we investigate the morphology, dynamics and mechanics of tumoroids using particle-based models of active dividing soft spheres. While cell motility has been modelled extensively using Active Brownian Particles (ABPs), tumoroids lack a 2D substrate and must obey action-reaction. We propose such a reciprocal activity, Pair ABP, and implement the extracellular matrix (ECM) as a soft passive gel. Pair ABP activity allows for cell-cell and cell-ECM "crawling". Simulations with SAMoS and wrapper cellSAMoS enable automated model execution, analysis, and visualisation. First, without the ECM, we compare ABPs to Pair ABPs and find 3D tumoroid reconfiguration driven by cell division and motility. We then study the clustering and glassy dynamics of a 2D...Show moreUnderstanding the collective migration in tumoroids, in-vitro tumour spheroids, provides insights into breast cancer metastasis. Recent observations by Schmidt et al. have revealed their intriguing mechanical and morphological properties. Here, we investigate the morphology, dynamics and mechanics of tumoroids using particle-based models of active dividing soft spheres. While cell motility has been modelled extensively using Active Brownian Particles (ABPs), tumoroids lack a 2D substrate and must obey action-reaction. We propose such a reciprocal activity, Pair ABP, and implement the extracellular matrix (ECM) as a soft passive gel. Pair ABP activity allows for cell-cell and cell-ECM "crawling". Simulations with SAMoS and wrapper cellSAMoS enable automated model execution, analysis, and visualisation. First, without the ECM, we compare ABPs to Pair ABPs and find 3D tumoroid reconfiguration driven by cell division and motility. We then study the clustering and glassy dynamics of a 2D plane filled with polydisperse active Pair ABPs. Upon implementing the 3D ECM gel, we find an asymmetric balance of cell division and ECM secretion. By varying the ECM density, cell-ECM stiffness, and cell motility, we analyse the mixing of an active-passive particle collective and spheroid unjamming. Our latest simulations resemble radial pressure and shear profiles from experiments. Overall, we demonstrate the potential of active matter for refining our understanding of tumoroid multicellular migration and potentially informing cancer treatment strategies.Show less

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Modelling Tumoroid Collective Migration: Interplay of Pair Active Brownian Motion and the ExtraCellular Matrix