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How do your neurons grow?


08 January 2008

How does a nerve cell find its way to the end of an elephant's trunk? US researchers could soon have the answer.

Andre Levchenko and co-workers at Johns Hopkins University, Baltimore, have created a grooved microfluidic chip that allows them to follow nerve cell growth in response to chemical signals. This directed growth is a key process in brain and nervous system regeneration and development. 

A lab on a chip method is used to follow nerve cell growth in multiple chemical gradients

A lab on a chip method is used to follow nerve cell growth in multiple chemical gradients

Nerve cells can span over a metre. During development or following injury, nerve cell axons have to navigate to a specific target as they grow. The growth is directed by the growing tip of the axon - the growth cone - and is guided by a variety of chemical and physical signposts, or cues. Replicating this complex environment in laboratory experiments has proved very challenging, especially as nerve cell growth is sensitive to shear forces in flowing liquids. 

Levchenko's new device overcomes this problem, allowing his team to investigate the effect of multiple guidance cues on nerve cell growth. The cells are housed in micro-grooves to protect them from shear stress and a series of channels allows the guidance cue amounts to be controlled precisely. By filming cell growth using high powered microscopes, the team was able to examine how multiple cue gradients affect axon growth direction. 

"One molecule modulates the response of the growth cone to another"
- David Juncker
David Juncker, an expert in microfluidics and bioengineering, at McGill University, in Montreal, Canada, explained that the researchers obtained an unexpected result: 'One molecule apparently modulates the response of the growth cone to another. This work nicely illustrates the advantages of microfluidics for studying how cells integrate multiple external cues.'

Looking to the future, Levchenko said that the research could be used to 'address the fundamental mechanism of how neurons respond to complex micro-environments. It could also find use in screening libraries of drugs and drug concentrations or in creating artificial neural networks within the chip.'

Russell Johnson

Link to journal article

A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues
C. Joanne Wang, Xiong Li, Benjamin Lin, Sangwoo Shim, Guo-li Ming and Andre Levchenko, Lab Chip, 2008, 8, 227
DOI: 10.1039/b713945d

Also of interest

Biomolecular gradients in cell culture systems
Thomas M. Keenan and Albert Folch, Lab Chip, 2008, 8, 34
DOI: 10.1039/b711887b

Gradient generation by an osmotic pump and the behavior of human mesenchymal stem cells under the fetal bovine serum concentration gradient
Joong Yull Park, Chang Mo Hwang, Soon Hyuck Lee and Sang-Hoon Lee, Lab Chip, 2007, 7, 1673
DOI: 10.1039/b710777c