Johns Hopkins researchers from the Whiting School of
Engineering and the School of Medicine
have devised a micro-scale tool — a "lab on a chip"
— designed to mimic the chemical complexities of the
brain.
The system should help scientists better understand
how nerve cells in the brain work together
to form the nervous system.
A report on the work appears as the cover story in the
February issue of the British journal Lab
on a Chip.
"The chip we've developed will make experiments on
nerve cells more simple to conduct and to
control," said Andre Levchenko, associate professor of
biomedical engineering at the Whiting School
and faculty affiliate of the university's Institute for
NanoBioTechnology.
Nerve cells decide which direction to grow by sensing
both the chemical cues flowing through
their environment and those attached to the surfaces that
surround them. The chip, which is made of
a plasticlike substance and covered with a glass lid,
features a system of channels and wells that allow
researchers to control the flow of specific chemical
cocktails around single nerve cells.
Guo-li Ming, associate professor of neurology at the
School of Medicine and Institute for Cell
Engineering, said, "It is difficult to establish ideal
experimental conditions to study how neurons react
to growth signals because so much is happening at once that
sorting out nerve cell connections is hard,
but the chip, designed by experts in both brain chemistry
and engineering, offers a sophisticated way
to sort things out."
In experiments, the researchers put single nerve
cells, or neurons, onto the chip, then
introduced specific growth signals (in the form of
chemicals). They found that the growing neurons
turned and grew toward higher concentrations of certain
chemical cues attached to the chip's
surfaces, as well as to signaling molecules free-flowing in
solution.
When researchers subjected the neurons to conflicting
signals (both surfacebound and cues in
solution), they found that the cells turned randomly,
suggesting that cells do not choose one signal
over the other. This, according to Levchenko, supports the
prevailing theory that one cue can elicit
different responses depending on a cell's surroundings.
"The ability to combine several different stimuli in
the chip resembles a more realistic
environment that nerve cells will encounter in the living
animal," Ming said. This, he said, will make
future studies on the role of neuronal cells in development
and regeneration more accurate and
complete.
The research was funded by the Johns Hopkins
institutes for NanoBiotechnology and
Cell
Engineering, the National Institutes of Health, March
of Dimes, a Klingenstein Fellowship Award and
the Alfred P. Sloan and Adelson Medical Research
foundations.
Authors on the paper are C. Joanne Wang, Xiong Li,
Benjamin Lin, Sangwoo Shim, Ming and
Levchenko, all of Johns Hopkins.