Filopodia: Nanodevices that sense nanotopographic ECM cues to orient neurite outgrowth

The processes of neuronal outgrowth and guidance have typically been studied in classic 2D cell culture systems that do not recapitulate topographical cues present in the in vivo extracellular matrix (ECM). Using microfabrication techniques, we mimicked this ECM topography by presenting laminin on a line pattern with nanometric size features. We found that this not only allows neurite orientation but also robust outgrowth. This depends on dynamic stochastic sensing of the line pattern by growth cone filopodia which allows them to probe their surrounding space by measuring the extent of filopodial adhesion surface with the ECM. Filopodium alignment with an ECM line allows to the formation of a robust F-actin network that leads to its stabilization, allowing steady neurite extension along the line pattern. Because this model system allows exquisitely stereotypic filopodial dynamics, this opens up the possibility to easily study the spatio-temporal dynamics of the signaling networks that regulate this prototypic growth cone navigation system.