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Stimulation of neural stem cell differentiation by circularly polarized light transduced by chiral nanoassemblies

Abstract

The biological effects of circularly polarized light on living cells are considered to be negligibly weak. Here, we show that the differentiation of neural stem cells into neurons can be accelerated by circularly polarized photons when DNA-bridged chiral assemblies of gold nanoparticles are entangled with the cells’ cytoskeletal fibres. By using cell-culture experiments and plasmonic-force calculations, we demonstrate that the nanoparticle assemblies exert a circularly-polarized-light-dependent force on the cytoskeleton, and that the light-induced periodic mechanical deformation of actin nanofibres with a frequency of 50 Hz stimulates the differentiation of neural stem cells into the neuronal phenotype. When implanted in the hippocampus of a mouse model of Alzheimer’s disease, neural stem cells illuminated following a polarity-optimized protocol reduced the formation of amyloid plaques by more than 70%. Our findings suggest that circularly polarized light can guide cellular development for biomedical use.

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Fig. 1: CPL accelerates NSCs differentiation.
Fig. 2: Neuron expression of differentiated NSCs under CPL illumination.
Fig. 3: Differentiation of NSCs under CPL illumination.
Fig. 4: Mechanism of NSC differentiation after CPL irradiation.
Fig. 5: Characterization of the chiral nanoassemblies entangled with cytoskeleton under CPL illumination.
Fig. 6: In vivo AD therapy through CPL-accelerated NSCs.
Fig. 7: Restoration of neurons and cognitive ability of AD mice by CPL-accelerated NSCs.

Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information. The raw data are available from figshare with the identifier https://doi.org/10.6084/m9.figshare.12931874.

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (grant nos. 21925402, 51802125 and 21631005). A part of this work (from N.A.K. and J.-Y.K.) was supported by NSF projects NSF 1463474, NSF 1566460 and DoD W911NF-10-1-0518.

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H.K., N.A.K. and C.X. conceived the project and designed the experiments. A.Q. and M.S. were responsible for cell and animal experiments. J.-Y.K. carried out the electromagnetic calculations. L.X. and C.H. carried out the assembly synthesis. W.M. and X.W. were responsible for spectroscopic measurements. H.K. and N.A.K. conceptualized the work. C.X. and H.K. supervised the study. H.K., N.A.K. and C.X. analysed the results and wrote the manuscript. X.L., H.K., N.A.K. and C.X. discussed the results and commented on the manuscript.

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Correspondence to Hua Kuang or Nicholas A. Kotov or Chuanlai Xu.

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Qu, A., Sun, M., Kim, JY. et al. Stimulation of neural stem cell differentiation by circularly polarized light transduced by chiral nanoassemblies. Nat Biomed Eng 5, 103–113 (2021). https://doi.org/10.1038/s41551-020-00634-4

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