Decoding complex transport patterns in flow-induced autologous chemotaxis of multicellular systems

Abstract

Cell migration via autologous chemotaxis in the presence of interstitial fluid flow is important in cancer metastasis and embryonic development. Despite significant recent progress, our understanding of flow-induced autologous chemotaxis of multicellular systems remains poor. The literature presents inconsistent findings regarding the effectiveness of collective autologous chemotaxis of densely packed cells under interstitial fluid flow. Here, we present a high-fidelity computational model to analyze the migration of multicellular systems performing autologous chemotaxis in the presence of interstitial fluid flow. Our simulations show that the details of the complex transport dynamics of the chemoattractant and fluid flow patterns that occur in the extracellular space, previously overlooked, are essential to understand this cell migration mechanism. We find that, although flow-induced autologous chemotaxis is a robust migration mechanism for individual cells, the cell-cell interactions that occur in multicellular systems render autologous chemotaxis an inefficient mechanism of collective cell migration. Our results offer new perspectives on the potential role of autologous chemotaxis in the tumor microenvironment, where fluid flow is an important modulator of transport.