Effects of surface asymmetry on neuronal growth

• Published in: PloS one Vol. 9; no. 9; p. e106709
• Main Authors: Spedden, Elise, Wiens, Matthew R, Demirel, Melik C, Staii, Cristian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.09.2014; Public Library of Science (PLoS)
• Subjects: Animal behavior; Animals; Anisotropy; Astronomy; Asymmetry; Axon guidance; Axons - physiology; Bias; Biology and Life Sciences; Cell adhesion & migration; Cell surface; Cells, Cultured; Coefficients; Cues; Cytoskeleton; Cytoskeleton - metabolism; Drift; Glass substrates; Growth; Kinases; Microscopy; Microtubules; Models, Biological; Myosin; Nervous system; Neurons; Normal distribution; Paclitaxel; Paclitaxel - pharmacology; Physical properties; Physical Sciences; Physics; Rats; Regeneration; Regeneration - drug effects; Signal transduction; Stochastic models; Stochastic Processes; Stochasticity; Studies; Substrates; Surface layers; Taxol; Texture; Topography; United States > US; Massachusetts; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106709

Detailed knowledge of how the surface physical properties, such as mechanics, topography and texture influence axonal outgrowth and guidance is essential for understanding the processes that control neuron development, the formation of functional neuronal connections and nerve regeneration. Here we synthesize asymmetric surfaces with well-controlled topography and texture and perform a systematic experimental and theoretical investigation of axonal outgrowth on these substrates. We demonstrate unidirectional axonal bias imparted by the surface ratchet-based topography and quantify the topographical guidance cues that control neuronal growth. We describe the growth cone dynamics using a general stochastic model (Fokker-Planck formalism) and use this model to extract two key dynamical parameters: diffusion (cell motility) coefficient and asymmetric drift coefficient. The drift coefficient is identified with the torque caused by the asymmetric ratchet topography. We relate the observed directional bias in axonal outgrowth to cellular contact guidance behavior, which results in an increase in the cell-surface coupling with increased surface anisotropy. We also demonstrate that the disruption of cytoskeletal dynamics through application of Taxol (stabilizer of microtubules) and Blebbistatin (inhibitor of myosin II activity) greatly reduces the directional bias imparted by these asymmetric surfaces. These results provide new insight into the role played by topographical cues in neuronal growth and could lead to new methods for stimulating neuronal regeneration and the engineering of artificial neuronal tissue.