Polymer Nanopillars Induce Increased Paxillin Adhesion Assembly and Promote Axon Growth in Primary Cortical Neurons

The complexity of the extracellular matrix consists of micro- and nanoscale structures that influence neuronal development through contact guidance. Substrates with defined topographic cues mimic the complex extracellular environment and can improve the interface between cells and biomedical devices as well as potentially serve as tissue engineering scaffolds. This study investigates axon development and growth of primary cortical neurons on OrmoComp nanopillars of various dimensions. Neuronal somas and neurites form adhesions and F-actin accumulations around the pillars indicating a close contact to the topography. In addition, higher pillars (400 nm) confine the growing neurites, resulting in greater neurite alignment to the topographical pattern compared to lower pillars (100 nm). A comprehensive analysis of growth cone dynamics during axon development shows that nanopillars induce earlier axon establishment and change the periodicity of growth cone dynamics by promoting elongation. This results in longer axons compared to the flat substrate. Finally, the increase in surface area available for growth cone coupling provided by nanopillar sidewalls is correlated with increased assembly of paxillin-rich point contact adhesions and a reduction in actin retrograde flow rates allowing for accelerated and persistent neurite outgrowth.

Automated summary

This study demonstrates that substrates with defined topographic cues can improve neuronal development and potentially serve as tissue engineering scaffolds by mimicking the complex extracellular environment. Higher nanopillars effectively confine growing neurites, promoting better alignment to the topographical pattern, resulting in longer axons. The nanopillars also induce earlier axon establishment and change the periodicity of growth cone dynamics, leading to longer axons compared to flat substrates.