Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

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.

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