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Mechanobiology of Disease
Poster Abstracts
92
62-POS
Board 62
Acoustic Mechanogenetics for Controlling Neuron Activity and Signaling
Zhihai Qiu
1
, Yaoheng Yang
1
, Jinghui Guo
2
, Shashwati Kala
1
, Hsiao Chang Chan
2
, Lei Sun
1
.
1
The Hong Kong Polytechnic University, Hung Hom, Hong Kong,
2
The Chinese University of
Hong Kong, Sha Tin, Hong Kong.
Mechanosensitive receptors and ion channels in neuron surface can sense the mechanical
properties in their microenvironment and mediate neuronal activity and signaling. However, how
these signals integrate with other signals such as chemical and spatial signal to give rise to
human thought and plasticity reminds elusive. The challenge is to develop a mechano-tool for
controlling the neuron activity and signaling non-invasively with high spatiotemporal resolution.
To date, we developed an ultrasonic mechanogenetic tool for quantitative and selective
manipulation of the neuron activity and signaling. Nano-gas vesicles (NGV) which can induce
highly localized mechano-perturbations in low intensity ultrasound fields, were functionalized
with ligands and antibodies to target specific mechanosensitive membrane proteins (e.g. TRPV1
and Piezo 1 channels etc.) on primary neurons. Neuron activities mediated by the targeted
oscillating NGV driven by ultrasound were investigated by calcium imaging and patch-clamp,
while the neuronal signaling especially calcium related signaling regulation and phosphorylation
were tested by Western blot. Our results showed that under low intensity ultrasound irradiation,
local ultrasound pressure will be significantly intensified and localized where the oscillating
NGV were placed. Furthermore, the intensity of the generated highly localized ultrasound field
depending on ultrasound intensity and frequency was able to activate the targeted
mechanosensitive proteins followed by inwards ion currents, calcium influx, and PKA up-
regulations. It achieves molecular selectivity with subcellular precision. Capable of non-invasive
transmission though the tissue with fine focal size to integrate other stimulation in the brain,
ultrasonic mechanogenetics is an encouraging means for investigating mechanobiology in brain
and a good alternative to existing stimulating strategies for studying brain function with the
advantages of non-invasiveness, fine spatial control, and deeper tissue penetration. We also
envision that it is an invaluable tool for studying cancer mechanobiology in vivo as well.