Molecular machines stimulate intercellular calcium waves and cause muscle contraction

Beckham, J. L.; van Venrooy, A. R.; Kim, S.; Li, G.; Li, B.; Duret, G.; Arnold, D.; Zhao, X.; Santos, A. L.; Chaudhry, G.; Robinson, J. T.; Tour, J.

doi:10.1101/2022.11.04.515191

bioRxiv · 10.1101/2022.11.04.515191

Molecular machines stimulate intercellular calcium waves and cause muscle contraction

Beckham, J. L.·van Venrooy, A. R.·Kim, S.·Li, G.·Li, B.·Duret, G.·Arnold, D.·Zhao, X.·Santos, A. L.·Chaudhry, G.·Robinson, J. T.·Tour, J.

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Abstract

Intercellular calcium waves (ICW) are complex signaling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression, and changes in neuronal excitability. Accordingly, the remote stimulation of ICW may result in versatile new biomodulation and therapeutic strategies. Here, we demonstrate that light-activated molecular machines (MM), molecules that rotate and perform mechanical work on the molecular scale, can remotely stimulate ICW. Live-cell calcium tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol triphosphate (IP3) mediated signaling pathways by unidirectional, fast-rotating MM. We then demonstrated that MM-induced ICW can be used to control muscle contraction in vitro in cardiomyocytes and animal behavior in vivo in Hydra vulgaris. Consequentially, this work demonstrates a new strategy for the direct control of cell signaling and downstream biological function using molecular-scale devices.

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Beckham, J. L., van Venrooy, A. R., Kim, S., Li, G., Li, B., Duret, G., Arnold, D., Zhao, X., Santos, A. L., Chaudhry, G., Robinson, J. T., Tour, J.. 2022-11-04. Molecular machines stimulate intercellular calcium waves and cause muscle contraction. https://doi.org/10.1101/2022.11.04.515191

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