BPS2026 – How to make axons grow fast

Axonal elongation is critical for neural development and regeneration, yet its underlying mechanisms and potential for therapeutic enhancement remain unclear. Here, we develop a unified active fluid model that links axonal outgrowth and cell crawling, processes that similarly operate through bulk cytoskeletal flow, adhesion dynamics, and force generation. The modeling shows axonal elongation rate depends on gradients in internal contractile forces, cytoskeletal viscosity, and substrate adhesion. It predicts that rapid extension is promoted by (1) reducing viscosity within the axon, (2) increasing contractile activity in the growth cone transition zone, (3) decreasing force generation along the axon shaft, and (4) tuning adhesion to avoid either over-anchoring or poor attachment. These predictions are based on and supported by experimental measurements of neuronal morphology, bulk flow, and effects of modulating substrate geometry and adhesiveness on outgrowth. Together, these results provide a unified framework for understanding cell migration and axonal growth as variations of the same physical process. Beyond clarifying fundamental mechanisms, the model identifies pharmacological and molecular strategies—such as modulation of non-muscle myosin II, Rap, Ran, and Rho family GTPases that may control outgrowth during development and accelerate it after injury. By bridging cellular and neuronal motility processes, this work provides a foundation for advancing regenerative medicine and biophysical research into neural dynamics.