Label-free detection of neuron-drug interactions using acoustic and Kelvin vibrational fields.
Kelvin and acoustic fields of high-frequency have been employed in the non-invasive investigation of immortalized hypothalamic neurons, in order to assess their response to different concentrations of specific drugs, toxins, a stress-reducing hormone and neurotrophic factors. In an analytical systems biology approach, this work constitutes a first study of living neuron cultures by scanning Kelvin nanoprobe (SKN) and thickness shear mode (TSM) acoustic wave techniques. N-38 hypothalamic mouse neurons were immobilized on the gold electrode of 9 MHz TSM acoustic wave devices and gold-coated slides for study by SKN. The neurons were exposed to the neurochemicals betaseron, forskolin, TCAP, and cerebrolysin. Signals were collected with the TSM in real-time mode, and with the SKN in scanning and real-time modes, as the drugs were applied at biologically significant concentrations. With the TSM, for all drugs, some frequency and resistance shifts were in the same direction, contrary to normal functioning for this type of instrument. Possible mechanisms are presented to explain this behaviour. An oscillatory signal with periodicity of approximately 2 min was observed for some neuron-coated surfaces, where the amplitude of these oscillations was altered upon application of certain neurotrophic factors. These two new techniques present novel and non-invasive electrodeless methods for detecting changes at the cellular level caused by a variety of neuroactive compounds, without killing or destroying the neurons.
Cheran
Larisa-Emilia
LE
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Cheung
Shilin
S
Al Chawaf
Arij
A
Ellis
Jonathan S
JS
Belsham
Denise D
DD
MacKay
William A
WA
Lovejoy
David
D
Thompson
Michael
M
D000162:Acoustics; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology*; D007155:Immunologic Factors / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology; D014732:Vibration
D000596:Amino Acids; D007155:Immunologic Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C500186:TCAP-1 protein, mouse; D014118:Toxins, Biological; D005576:Colforsin; C006952:cerebrolysin; D016899:Interferon-beta