PMID- 18231660
OWN - NLM
STAT- MEDLINE
DCOM- 20080401
LR  - 20080130
IS  - 1473-0197 (Print)
IS  - 1473-0189 (Linking)
VI  - 8
IP  - 2
DP  - 2008 Feb
TI  - A microfluidics-based turning assay reveals complex growth cone responses to 
      integrated gradients of substrate-bound ECM molecules and diffusible guidance 
      cues.
PG  - 227-37
LID - 10.1039/b713945d [doi]
AB  - Neuronal growth cones contain sophisticated molecular machinery precisely 
      regulating their migration in response to complex combinatorial gradients of 
      diverse external cues. The details of this regulation are still largely unknown, 
      in part due to limitations of the currently available experimental techniques. 
      Microfluidic devices have been shown to be capable of generating complex, stable 
      and precisely controlled chemical gradients, but their use in studying growth 
      cone migration has been limited in part due to the effects of shear stress. Here 
      we describe a microfluidics-based turning-assay chip designed to overcome this 
      issue. In addition to generating precise gradients of soluble guidance cues, the 
      chip can also fabricate complex composite gradients of diffusible and 
      surface-bound guidance cues that mimic the conditions the growth cones 
      realistically counter in vivo. Applying this assay to Xenopus embryonic spinal 
      neurons, we demonstrate that the presence of a surface-bound laminin gradient can 
      finely tune the polarity of growth cone responses (repulsion or attraction) to 
      gradients of brain-derived neurotrophic factor (BDNF), with the guidance outcome 
      dependent on the mean BDNF concentration. The flexibility inherent in this assay 
      holds significant potential for refinement of our understanding of nervous system 
      development and regeneration, and can be extended to elucidate other cellular 
      processes involving chemotaxis of shear sensitive cells.
FAU - Joanne Wang, C
AU  - Joanne Wang C
AD  - Department of Biomedical Engineering and Whitaker Institute of Biomedical 
      Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 
      21218, USA.
FAU - Li, Xiong
AU  - Li X
FAU - Lin, Benjamin
AU  - Lin B
FAU - Shim, Sangwoo
AU  - Shim S
FAU - Ming, Guo-Li
AU  - Ming GL
FAU - Levchenko, Andre
AU  - Levchenko A
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080104
PL  - England
TA  - Lab Chip
JT  - Lab on a chip
JID - 101128948
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dimethylpolysiloxanes)
RN  - 0 (Laminin)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/chemistry/*pharmacology
MH  - Diffusion
MH  - Dimethylpolysiloxanes/chemistry
MH  - Equipment Design
MH  - Extracellular Matrix/*chemistry
MH  - Growth Cones/*drug effects
MH  - Laminin/chemistry/*pharmacology
MH  - Microfluidics/*instrumentation/*methods
MH  - Neurons/drug effects/ultrastructure
MH  - Solubility
MH  - Spinal Cord/cytology/embryology
MH  - Surface Properties
MH  - Xenopus/embryology
EDAT- 2008/01/31 09:00
MHDA- 2008/04/02 09:00
CRDT- 2008/01/31 09:00
PHST- 2008/01/31 09:00 [pubmed]
PHST- 2008/04/02 09:00 [medline]
PHST- 2008/01/31 09:00 [entrez]
AID - 10.1039/b713945d [doi]
PST - ppublish
SO  - Lab Chip. 2008 Feb;8(2):227-37. doi: 10.1039/b713945d. Epub 2008 Jan 4.