Actin waves guide an outward movement of microclusters in the lymphocyte immunological synapse

Modelling approach: Agent based modelling

Exact description: Agent based modelling coupled with experimental data. TCR are modelled as agents that interact with set rules depending on the dynamics of experimentally observed actin features.

This model examines whether T cell receptor (TCR) microclusters are transported by actin waves or by the underlying actin flow. Building on previous analyses of TCR–actin coupling models (Refs. 1,2), it introduces a framework to quantify how the actin cytoskeleton influences anterograde TCR movement—a previously uncharacterized feature.

TCRs are modeled as tracer particles with a default retrograde motion toward the cell center. In mode 1, TCRs bind to actin wave features in their vicinity identified from experimental images via edge detection and move with the waves while these features are present. When no waves are present in the vicinity of the TCR, they revert to retrograde motion. In mode 2, particle image velocimetry (PIV) of actin flow fields determines local velocities; each TCR moves according to the average PIV vector in its vicinity. If PIV features are not detected in the vicinity of TCR, they again follow their default retrograde path.

TCR dynamics are compared with experimental results by analyzing the distributions of outward movement times, which represent the durations over which the TCR moves outward during its entire trajectory. To improve statistical robustness, trajectories are pooled by running the model across multiple actin datasets, along with several random realizations for each dataset.

Regulation of T-cell receptor signaling by the actin cytoskeleton and poroelastic cytoplasm. Immunol Rev 256:148–159.