Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. 1.

    Paviolo, C. et al. Laser exposure of gold nanorods can increase neuronal cell outgrowth. Biotechnol. Bioeng. 110, 2277–2291 (2013).

    CAS  PubMed  Google Scholar 

  2. 2.

    Baba, J. S., Chung, J. R., DeLaughter, A. H., Cameron, B. D. & Cote, G. L. Development and calibration of an automated Mueller matrix polarization imaging system. J. Biomed. Opt. 7, 341–349 (2002).

    PubMed  Google Scholar 

  3. 3.

    Funck, T., Nicoli, F., Kuzyk, A. & Liedl, T. Sensing picomolar concentrations of RNA using switchable plasmonic chirality. Angew. Chem. Int. Ed. 57, 13495–13498 (2018).

    CAS  Google Scholar 

  4. 4.

    Hendry, E. et al. Ultrasensitive detection and characterization of biomolecules using superchiral fields. Nat. Nanotechnol. 5, 783–787 (2010).

    CAS  PubMed  Google Scholar 

  5. 5.

    Chen, W. et al. Nanoparticle superstructures made by polymerase chain reaction: collective interactions of nanoparticles and a new principle for chiral materials. Nano Lett. 9, 2153–2159 (2009).

    CAS  PubMed  Google Scholar 

  6. 6.

    Zhao, X. et al. Tuning the interactions between chiral plasmonic films and living cells. Nat. Commun. 8, 2007 (2017).

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Patel, M., Moon, H. J., Hong, J. H. & Jeong, B. Chiro-optical modulation for NURR1 production from stem cells. ACS Chem. Neurosci. 8, 1455–1458 (2017).

    CAS  PubMed  Google Scholar 

  8. 8.

    Morrow, S. M., Bissette, A. J. & Fletcher, S. P. Transmission of chirality through space and across length scales. Nat. Nanotechnol. 12, 410–419 (2017).

    CAS  PubMed  Google Scholar 

  9. 9.

    Vestler, D. et al. Circular dichroism enhancement in plasmonic nanorod metamaterials. Opt. Express 26, 17841–17848 (2018).

    CAS  PubMed  Google Scholar 

  10. 10.

    Govan, J. & Gun’ko, Y. K. in Nanoscience Vol. 3, 1–30 (Royal Society of Chemistry, 2016).

  11. 11.

    Auguié, B., Alonso-Gómez, J. L., Guerrero-Martínez, A. & Liz-Marzán, L. M. Fingers crossed: optical activity of a chiral dimer of plasmonic nanorods. J. Phys. Chem. Lett. 2, 846–851 (2011).

    PubMed  Google Scholar 

  12. 12.

    Sun, M. et al. Intracellular localization of nanoparticle dimers by chirality reversal. Nat. Commun. 8, 1847 (2017).

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Ma, W. et al. Chiral inorganic nanostructures. Chem. Rev. 117, 8041–8093 (2017).

    CAS  PubMed  Google Scholar 

  14. 14.

    Zhou, L. A. et al. Quantifying hot carrier and thermal contributions in plasmonic photocatalysis. Science 362, 69–72 (2018).

    CAS  PubMed  Google Scholar 

  15. 15.

    Sun, M. Z. et al. Site-selective photoinduced cleavage and profiling of DNA by chiral semiconductor nanoparticles. Nat. Chem. 10, 821–830 (2018).

    CAS  PubMed  Google Scholar 

  16. 16.

    Li, S. et al. Single- and multi-component chiral supraparticles as modular enantioselective catalysts. Nat. Commun. 10, 4826 (2019).

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Kim, J.-Y. et al. Assembly of gold nanoparticles into chiral superstructures driven by circularly polarized light. J. Am. Chem. Soc. 141, 11739–11744 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Valev, V. K. et al. Nanostripe length dependence of plasmon-induced material deformations. Opt. Lett. 38, 2256–2258 (2013).

    PubMed  Google Scholar 

  19. 19.

    Laramy, C. R., O’Brien, M. N. & Mirkin, C. A. Crystal engineering with DNA. Nat. Rev. Mater. 4, 201–224 (2019).

    CAS  Google Scholar 

  20. 20.

    Chen, G. et al. Regioselective surface encoding of nanoparticles for programmable self-assembly. Nat. Mater. 18, 169–174 (2019).

    CAS  PubMed  Google Scholar 

  21. 21.

    Leung, K., Chakraborty, K., Saminathan, A. & Krishnan, Y. A DNA nanomachine chemically resolves lysosomes in live cells. Nat. Nanotechnol. 14, 176–183 (2019).

    CAS  PubMed  Google Scholar 

  22. 22.

    Zhang, Q. F. et al. Unraveling the origin of chirality from plasmonic nanoparticle–protein complexes. Science 365, 1475–1478 (2019).

    CAS  PubMed  Google Scholar 

  23. 23.

    Lu, D. R., Zhou, J. J., Chen, Y. H., Ma, J. L. & Duan, H. W. Self-assembly of polymer-coated plasmonic nanocrystals: from synthetic approaches to practical applications. Macromol. Rapid Commun. 40, 1800613 (2019).

    Google Scholar 

  24. 24.

    Ben-Moshe, A., Maoz, B., Govorov, A. O. & Markovich, G. Chirality and chiroptical effects in inorganic nanocrystal systems with plasmon and exciton resonances. Chem. Soc. Rev. 42, 7028–7041 (2013).

    CAS  PubMed  Google Scholar 

  25. 25.

    Verma, A. et al. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nat. Mater. 7, 588–595 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Samanta, D., Ebrahimi, S. B. & Mirkin, C. A. Nucleic‐acid structures as intracellular probes for live cells. Adv. Mater. 32, 1901743 (2019).

    Google Scholar 

  27. 27.

    Wang, Z. et al. Bioinspired nanocomplex for spatiotemporal imaging of sequential mRNA expression in differentiating neural stem cells. ACS Nano 8, 12386–12396 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Calza, L., Fernandez, M., Giuliani, A., Aloe, L. & Giardino, L. Thyroid hormone activates oligodendrocyte precursors and increases a myelin-forming protein and NGF content in the spinal cord during experimental allergic encephalomyelitis. Proc. Natl Acad. Sci. USA 99, 3258–3263 (2002).

    CAS  PubMed  Google Scholar 

  29. 29.

    Solanki, A., Shah, S., Yin, P. T. & Lee, K.-B. Nanotopography-mediated reverse uptake for siRNA delivery into neural stem cells to enhance neuronal differentiation. Sci. Rep. 3, 1553 (2013).

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Johnson, G. V. W. & Jope, R. S. The role of microtubule-associated protein-2 (Map-2) in neuronal growth, plasticity and degeneration. J. Neurosci. Res. 33, 505–512 (1992).

    CAS  PubMed  Google Scholar 

  31. 31.

    Gu, H., Yu, S. P., Gutekunst, C.-A., Gross, R. E. & Wei, L. Inhibition of the Rho signaling pathway improves neurite outgrowth and neuronal differentiation of mouse neural stem cells. Int. J. Physiol. Pathophysiol. Pharmacol. 5, 11–20 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Garland, P., Quraishe, S., French, P. & O’Connor, V. Expression of the MAST family of senone/threonine kinases. Brain Res. 1195, 12–19 (2008).

    CAS  PubMed  Google Scholar 

  33. 33.

    Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

    Google Scholar 

  34. 34.

    Brusatin, G., Panciera, T., Gandin, A., Citron, A. & Piccolo, S. Biomaterials and engineered microenvironments to control YAP/TAZ-dependent cell behaviour. Nat. Mater. 17, 1063–1075 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Xue, X. F. et al. Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells. Nat. Mater. 17, 633–641 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Cui, Y. et al. Cyclic stretching of soft substrates induces spreading and growth. Nat. Commun. 6, 6333 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Asbury, C. L., Gestaut, D. R., Powers, A. F., Franck, A. D. & Davis, T. N. The Dam1 kinetochore complex harnesses microtubule dynamics to produce force and movement. Proc. Natl Acad. Sci. USA 103, 9873–9878 (2006).

    CAS  PubMed  Google Scholar 

  38. 38.

    Kreplak, L., Herrmann, H. & Aebi, U. Tensile properties of single desmin intermediate filaments. Biophys. J. 94, 2790–2799 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Guolla, L., Bertrand, M., Haase, K. & Pelling, A. E. Force transduction and strain dynamics in actin stress fibres in response to nanonewton forces. J. Cell Sci. 125, 603–613 (2012).

    CAS  PubMed  Google Scholar 

  40. 40.

    Shafrir, Y. & Forgacs, G. Mechanotransduction through the cytoskeleton. Am. J. Physiol. Cell Physiol. 282, C479–C486 (2002).

    CAS  PubMed  Google Scholar 

  41. 41.

    Juan, M. L., Righini, M. & Quidant, R. Plasmon nano-optical tweezers. Nat. Photon. 5, 349–356 (2011).

    CAS  Google Scholar 

  42. 42.

    Karafyllidis, I. G. & Lagoudas, D. C. Microtubules as mechanical force sensors. Biosystems 88, 137–146 (2007).

    CAS  PubMed  Google Scholar 

  43. 43.

    Fletcher, D. A. & Mullins, R. D. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Torii, T. et al. Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension. Cell. Signal. 24, 1872–1882 (2012).

    CAS  PubMed  Google Scholar 

  45. 45.

    Tee, Y. H. et al. Cellular chirality arising from the self-organization of the actin cytoskeleton. Nat. Cell Biol. 17, 445–457 (2015).

    CAS  PubMed  Google Scholar 

  46. 46.

    Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 560, 185–191 (2018).

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Rice, H. C. et al. Secreted amyloid-β precursor protein functions as a GABABR1a ligand to modulate synaptic transmission. Science 363, eaao4827 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


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.

Author information




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.

Corresponding authors

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

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary methods, figures, tables and references.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing