# Amoeboid-mesenchymal migration plasticity promotes invasion only in complex heterogeneous microenvironments

## TL;DR

This study uses a mathematical model to show that amoeboid-mesenchymal migration plasticity enhances tumor invasion only in complex, heterogeneous microenvironments with chemotactic gradients, highlighting the importance of environmental factors.

## Contribution

The paper introduces a mathematical model demonstrating that migration plasticity promotes invasion specifically in complex microenvironments, emphasizing the role of heterogeneity and chemical gradients.

## Key findings

- Migration plasticity enhances invasion in complex environments
- Heterogeneity and chemotactic gradients are key determinants
- In vitro studies should consider environmental complexity

## Abstract

During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that \emph{in vitro} systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.