Topographic cues of nano‐scale height direct neuronal growth pattern

We study the role of nano‐scale cues in controlling neuronal growth. We use photolithography to fabricate substrates with repeatable line‐pattern ridges of nano‐scale heights. We find that neuronal processes, which are of micron size, have strong interactions with ridges even as low as 10 nm. The interaction between the neuronal process and the ridge leads to a deflection of growth direction and a preferred alignment with the ridges. The interaction strength clearly depends on the ridges' height. For 25 nm ridges approximately half of the neuronal processes are modified, while at 100 nm the majority of neurites change their original growth direction post interaction. In addition, the effect on growth correlates with the incoming angle between the neuronal process and the ridge. We underline the adhesion as a key mechanism in directing neuronal growth. Our study highlights the sensitivity of growing neurites to nano‐scale cues thus opens a new avenue of research for pre‐designed neuronal growth and circuitry. Biotechnol. Bioeng. 2012; 109:1791–1797. © 2012 Wiley Periodicals, Inc.

[1]  Amir Ayali,et al.  The regulative role of neurite mechanical tension in network development. , 2009, Biophysical journal.

[2]  Boris Hofmann,et al.  Axon guidance of rat cortical neurons by microcontact printed gradients. , 2011, Biomaterials.

[3]  A Curtis,et al.  Topographical control of cells. , 1997, Biomaterials.

[4]  A F von Recum,et al.  Orientation of ECM protein deposition, fibroblast cytoskeleton, and attachment complex components on silicone microgrooved surfaces. , 1998, Journal of biomedical materials research.

[5]  Jae Young Lee,et al.  Hippocampal neurons respond uniquely to topographies of various sizes and shapes , 2010, Biofabrication.

[6]  S. Britland,et al.  Contact guidance of CNS neurites on grooved quartz: influence of groove dimensions, neuronal age and cell type. , 1997, Journal of cell science.

[7]  Stephen Britland,et al.  Morphogenetic guidance cues can interact synergistically and hierarchically in steering nerve cell growth , 1996 .

[8]  Lars Montelius,et al.  Axonal outgrowth on nano-imprinted patterns. , 2006, Biomaterials.

[9]  Bruce C Wheeler,et al.  Designing Neural Networks in Culture: Experiments are described for controlled growth, of nerve cells taken from rats, in predesigned geometrical patterns on laboratory culture dishes. , 2010, Proceedings of the IEEE. Institute of Electrical and Electronics Engineers.

[10]  L. Reichardt,et al.  Control of axonal branching and synapse formation by focal adhesion kinase , 2004, Nature Neuroscience.

[11]  Ralph G Nuzzo,et al.  Textural Guidance Cues for Controlling Process Outgrowth of Mammalian Neurons † , 2008 .

[12]  A. B. Huber,et al.  Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. , 2003, Annual review of neuroscience.

[13]  Chong Xie,et al.  Noninvasive neuron pinning with nanopillar arrays. , 2010, Nano letters.

[14]  Andre Levchenko,et al.  Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs , 2009, Proceedings of the National Academy of Sciences.

[15]  Bruce C. Wheeler,et al.  Designing Neural Networks in Culture , 2010, Proceedings of the IEEE.

[16]  Amir Harel,et al.  Biophysical Constraints on Neuronal Branching , 2003, Neurocomputing.

[17]  Michael Thompson,et al.  Coupling of neurons with biosensor devices for detection of the properties of neuronal populations. , 2008, Chemical Society reviews.

[18]  P. Milani,et al.  Direct microfabrication of topographical and chemical cues for the guided growth of neural cell networks on polyamidoamine hydrogels. , 2010, Macromolecular bioscience.

[19]  Yoonkey Nam,et al.  Direct rapid prototyping of PDMS from a photomask film for micropatterning of biomolecules and cells. , 2009, Lab on a chip.

[20]  P. Forscher,et al.  Substrate-cytoskeletal coupling as a mechanism for the regulation of growth cone motility and guidance. , 2000, Journal of neurobiology.

[21]  P. Whitington,et al.  Axon guidance factors in invertebrate development. , 1993, Pharmacology & therapeutics.

[22]  C. McCaig,et al.  Guidance of CNS growth cones by substratum grooves and ridges: effects of inhibitors of the cytoskeleton, calcium channels and signal transduction pathways. , 1997, Journal of cell science.

[23]  C. Wilkinson,et al.  Topographical control of cell behaviour: II. Multiple grooved substrata. , 1990, Development.

[24]  R. G. Richards,et al.  Nanotopographical modification: a regulator of cellular function through focal adhesions. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[25]  W. Saltzman,et al.  The influence of microchannels on neurite growth and architecture. , 2005, Biomaterials.

[26]  Lars Montelius,et al.  Gallium phosphide nanowires as a substrate for cultured neurons. , 2007, Nano letters.

[27]  Lars Montelius,et al.  Axonal guidance on patterned free-standing nanowire surfaces , 2008, Nanotechnology.

[28]  B. Ju,et al.  Topographical guidance of mouse neuronal cell on SiO2 microtracks , 2007 .