Studies on neuron responses to simultaneous and competing extracellular cues
Abstract
The understanding of cell responses to extracellular signals is a field of
major importance. In particular, cell interactions with designed surfaces are
fundamental for creating successful interfaces between biomaterials and
biological entities. Bioactive materials that promote specific behaviors such as
cell proliferation, migration or differentiation are highly relevant for tissue
engineering strategies. In particular, neural engineering applications including
nerve conduits for nerve regeneration, neural prosthetics and artificial neural
networks, would be highly benefited from studies on artificial substrates that
modulate neuronal behavior.
Extracellular stimuli influence critical phases in neuronal development
such as neuron polarization (i.e., axon formation) and axon growth. There are
numerous stimuli that have been studied for influencing neuron responses. Some
of these stimuli are substrate topography, growth factors, extracellular matrix
components, electrical activity and the presence of support cells. Although all
these stimuli induce responses in neurons independently, in this investigation we
focused on cell behavior when simultaneous cues were presented to the cell.
This included both combinatorial and competitive cues.
We studied the novel combination of chemical and physical stimuli by
immobilizing nerve growth factor (NGF) on topographical features. We found that
topography (i.e., physical stimulus) highly influences axon formation, whereas
axon extension is controlled by a synergy of immobilized NGF and topography.
We also investigated the combination of electrical and chemical stimulation. In
that case, NGF was immobilized on polypyrrole, an electrically- conducting
polymer, finding an enhanced effect on neurite extension. Finally, simultaneous
but spatially independent stimuli (i.e., competitive stimuli) were investigated for
influencing direction of polarization. We found that physical cues were preferred
over chemical cues for axon formation.
Our results have contributed to further knowledge regarding the
modification of artificial substrates that better control neuronal responses. This
knowledge can be applied in the design of materials for nerve regeneration
strategies, the modification of electrodes that stimulate neurons in prosthetic
devices, and for the control of neuronal mapping and connectivity in neural nets.
Department
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