Molecular machines stimulate intercellular calcium waves and cause muscle contraction.

Nature nanotechnology 2023 Sep

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Intercellular calcium waves (ICW) are complex signalling 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 could result in versatile biomodulation and therapeutic strategies. Here we demonstrate that light-activated molecular machines (MM)-molecules that perform mechanical work on the molecular scale-can remotely stimulate ICW. MM consist of a polycyclic rotor and stator that rotate around a central alkene when activated with visible light. Live-cell calcium-tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol-triphosphate-mediated signalling pathways by unidirectional, fast-rotating MM. Our data suggest that MM-induced ICW can control muscle contraction in vitro in cardiomyocytes and animal behaviour in vivo in Hydra vulgaris. This work demonstrates a strategy for directly controlling cell signalling and downstream biological function using molecular-scale devices. © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Jacob L Beckham, Alexis R van Venrooy, Soonyoung Kim, Gang Li, Bowen Li, Guillaume Duret, Dallin Arnold, Xuan Zhao, John T Li, Ana L Santos, Gautam Chaudhry, Dongdong Liu, Jacob T Robinson, James M Tour. Molecular machines stimulate intercellular calcium waves and cause muscle contraction. Nature nanotechnology. 2023 Sep;18(9):1051-1059