# Modelling chemotaxis of branched cells in complex environments provides insights into immune cell navigation

## TL;DR

This study uses a theoretical model to understand how immune cells navigate complex environments using chemical signals, revealing a trade-off between speed and accuracy in their movement.

## Contribution

A novel theoretical model of branched cell chemotaxis in complex environments, validated with experimental data on neutrophil migration.

## Key findings

- The model captures subcellular responses and large-scale migration patterns of neutrophils in complex environments.
- Neutrophils operate in a fast regime, prioritizing speed over directional accuracy in weak chemical gradients.
- Internal cellular noise reduces the trade-off between speed and accuracy in chemotactic navigation.

## Abstract

Cell migration in vivo is often guided by chemical signaling, i.e., chemotaxis. For immune cells performing chemotaxis in the organism, this process is influenced by the complex geometry of the tissue environment. In this study, we use a theoretical model of branched cell migration on a network to explore the cellular response to chemical gradients. The model predicts the response of a branched cell to a chemical gradient: how the cell reorients its internal polarity and how it navigates through a complex environment up a chemical gradient. We then compare the model’s predictions with experimental observations of neutrophils migrating to the site of a laser-inflicted wound in a zebrafish larva fin, and neutrophils migrating in vitro inside a regular lattice of pillars. We find that the model captures the details of the subcellular response to the chemokine gradient, as well as qualitative characteristics of the large-scale migration, suggesting that the neutrophils behave as fast cells, which explains the functionality of these immune cells.

Cells often migrate through complex tissue environments by following chemical signals, a process known as chemotaxis. Immune cells like neutrophils, must rapidly navigate through complex tissue structures to reach sites of injury or infection. While migrating, these immune cells become highly branched, with multiple protrusions extending in-between the surrounding tissue cells. Here, we develop a theoretical model that describes how branched cells migrate in a network in response to chemical gradients. The model reveals a trade-off between speed and accuracy under low internal cellular noise: slower cells follow weak gradients more precisely, whereas faster cells reach the target more rapidly but with reduced directional accuracy. However, this relationship becomes much less pronounced in the presence of realistic levels of noise. We validate our model by comparing it to experiments of neutrophils migrating to a wound in zebrafish tissue and within a controlled lattice of micro-pillars. The data suggest that neutrophils operate in a fast regime, enabling rapid responses at the cost of accuracy in weak gradients. This study offers new insights into how immune cells respond to chemotactic gradients in complex environments, and provides a novel theoretical framework for understanding branched cell chemotaxis in vivo.