1.Guangdong Provincial Key Laboratory of Nanophotonic Manipulation, Institute of Nanophotonics, College of Physics and Optoelectronic Engineering, Jinan University, Guangzhou 511443, China
2.Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China
Baojun Li (baojunli@jnu.edu.cn)
Hongbao Xin (hongbaoxin@jnu.edu.cn)
Published:30 November 2024,
Published Online:19 September 2024,
Received:29 March 2024,
Revised:26 August 2024,
Accepted:29 August 2024
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Zhu, G. S. et al. Neural stimulation and modulation with sub-cellular precision by optomechanical bio-dart. Light: Science & Applications, 13, 2668-2679 (2024).
Zhu, G. S. et al. Neural stimulation and modulation with sub-cellular precision by optomechanical bio-dart. Light: Science & Applications, 13, 2668-2679 (2024). DOI: 10.1038/s41377-024-01617-9.
Neural stimulation and modulation at high spatial resolution are crucial for mediating neuronal signaling and plasticity
aiding in a better understanding of neuronal dysfunction and neurodegenerative diseases. However
developing a biocompatible and precisely controllable technique for accurate and effective stimulation and modulation of neurons at the subcellular level is highly challenging. Here
we report an optomechanical method for neural stimulation and modulation with subcellular precision using optically controlled bio-darts. The bio-dart is obtained from the tip of sunflower pollen grain and can generate transient pressure on the cell membrane with submicrometer spatial resolution when propelled by optical scattering force controlled with an optical fiber probe
which results in precision neural stimulation via precisely activation of membrane mechanosensitive ion channel. Importantly
controllable modulation of a single neuronal cell
even down to subcellular neuronal structures such as dendrites
axons
and soma
can be achieved. This bio-dart can also serve as a drug delivery tool for multifunctional neural stimulation and modulation. Remarkably
our optomechanical bio-darts can also be used for in vivo neural stimulation in larval zebrafish. This strategy provides a novel approach for neural stimulation and modulation with sub-cellular precision
paving the way for high-precision neuronal plasticity and neuromodulation.
Long, J. M.&Holtzman, D. M. Alzheimer disease: an update on pathobiology and treatment strategies.Cell179, 312–339 (2019)..
Dawson, T. M.&Dawson, V. L. Neuroprotective and neurorestorative strategies for Parkinson's disease.Nat. Neurosci.5, 1058–1061 (2002)..
Taylor, J. P., Brown, R. H.&Cleveland, D. W. Decoding ALS: from genes to mechanism.Nature539, 197–206 (2016)..
Wilson, D. M. et al. Hallmarks of neurodegenerative diseases.Cell186, 693–714 (2023)..
Won, S. M. et al. Emerging modalities and implantable technologies for neuromodulation.Cell181, 115–135 (2020)..
Shi, L. L. et al. Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter.Light Sci. Appl.10, 143 (2021)..
Jiang, Y. et al. Neural stimulation in vitro and in vivo by photoacoustic nanotransducers.Matter4, 654–674 (2021)..
Perlmutter, J. S.&Mink, J. W. Deep brain stimulation.Annu. Rev. Neurosci.29, 229–257 (2006)..
Lozano, A. M. et al. Deep brain stimulation: current challenges and future directions.Nat. Rev. Neurol.15, 148–160 (2019)..
Wagner, T., Valero-Cabre, A.&Pascual-Leone, A. Noninvasive human brain stimulation.Annu. Rev. Biomed. Eng.9, 527–565 (2007)..
Zangen, A. et al. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil.Clin. Neurophysiol.116, 775–779 (2005)..
Rabut, C. et al. Ultrasound technologies for imaging and modulating neural activity.Neuron108, 93–110 (2020)..
Yoo, S. et al. Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification.Nat. Commun.13, 493 (2022)..
Legon, W. et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.Nat. Neurosci.17, 322–329 (2014)..
De Boer, W. D. A. M. et al. Neuronal photoactivation through second-harmonic near-infrared absorption by gold nanoparticles.Light Sci. Appl.7, 100 (2018)..
Xin, H. B. et al. Optically controlled living micromotors for the manipulation and disruption of biological targets.Nano Lett.20, 7177–7185 (2020)..
Huang, Y. X. et al. Bioresorbable thin-film silicon diodes for the optoelectronic excitation and inhibition of neural activities.Nat. Biomed. Eng.7, 486–498 (2023)..
Xiong, J. Y. et al. Wake-riding effect-inspired opto-hydrodynamic diatombot for non-invasive trapping and removal of Nano-biothreats.Adv. Sci.10, 2301365 (2023)..
Stoev, I. D. et al. Highly sensitive force measurements in an optically generated, harmonic hydrodynamic trap.eLight1, 7 (2021)..
Liang, T. et al. Yoctonewton force detection based on optically levitated oscillator.Fundamental Res.3, 57–62 (2023)..
Vasquez-Lopez, S. A. et al. Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber.Light Sci. Appl.7, 110 (2018)..
Tao, L. C. et al. Microglia modulation with 1070-nm light attenuates Aβ burden and cognitive impairment in Alzheimer's disease mouse model.Light Sci. Appl.10, 179 (2021)..
Yizhar, O. et al. Optogenetics in neural systems.Neuron71, 9–34 (2011)..
Deisseroth, K. Optogenetics: 10 years of microbial opsins in neuroscience.Nat. Neurosci.18, 1213–1225 (2015)..
Emiliani, V. et al. Optogenetics for light control of biological systems.Nat. Rev. Methods Prim.2, 55 (2022)..
Fenno, L., Yizhar, O.&Deisseroth, K. The development and application of optogenetics.Annu. Rev. Neurosci.34, 389–412 (2011)..
Liu, X. et al. Nonthermal and reversible control of neuronal signaling and behavior by midinfrared stimulation.Proc. Natl Acad. Sci. USA118, e2015685118 (2021)..
Cheng, P. et al. Direct control of store-operated calcium channels by ultrafast laser.Cell Res.31, 758–772 (2021)..
Zhao, X. T. et al. In situ single-cell surgery and intracellular organelle manipulation via thermoplasmonics combined optical trapping.Nano Lett.22, 402–410 (2022)..
Minopoli, A. et al. ISO-FLUCS: symmetrization of optofluidic manipulations in quasi-isothermal micro-environments.eLight3, 16 (2023)..
Jiang, Y. et al. Optoacoustic brain stimulation at submillimeter spatial precision.Nat. Commun.11, 881 (2020)..
Li, Y. M. et al. Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision.Light Sci. Appl.11, 321 (2022)..
Fan, T. F. et al. Transformation of hard pollen into soft matter.Nat. Commun.11, 1449 (2020)..
Sun, M. M. et al. Autonomous biohybrid urchin-like microperforator for intracellular payload delivery.Small16, 1906701 (2020)..
Wang, J. et al. Physical activation of innate immunity by spiky particles.Nat. Nanotechnol.13, 1078–1086 (2018)..
Li, X. et al. Opto-hydrodynamic driven 3D dynamic microswarm petals.Laser Photonics Rev.18, 2300480 (2024)..
Chen, Y. D. et al. Carbon helical nanorobots capable of cell membrane penetration for single cell targeted SERS bio-sensing and photothermal cancer therapy.Adv. Funct. Mater.32, 2200600 (2022)..
Gao, W. et al. Catalytic iridium-based Janus micromotors powered by ultralow levels of chemical fuels.J. Am. Chem. Soc.136, 2276–2279 (2014)..
Xiong, J. Y. et al. Light-controlled soft bio-microrobot.Light Sci. Appl.13, 55 (2024)..
Pan, T. et al. Bio-Micromotor tweezers for noninvasive bio-cargo delivery and precise therapy.Adv. Funct. Mater.32, 2111038 (2022)..
Wu, J., Goyal, R.&Grandl, J. Localized force application reveals mechanically sensitive domains of Piezo1.Nat. Commun.7, 12939 (2016)..
Liu, Y. R. et al. Light-driven single-cell rotational adhesion frequency assay.eLight2, 13 (2022)..
Jin, P., Jan, L. Y.&Jan, Y. N. Mechanosensitive ion channels: structural features relevant to mechanotransduction mechanisms.Annu. Rev. Neurosci.43, 207–229 (2020)..
Ciofani, G. et al. Enhancement of neurite outgrowth in neuronal-like cells following boron nitride nanotube-mediated stimulation.ACS Nano4, 6267–6277 (2010)..
Gaub, B. M. et al. Neurons differentiate magnitude and location of mechanical stimuli.Proc. Natl Acad. Sci. USA117, 848–856 (2019)..
Gregurec, D. et al. Magnetic vortex nanodiscs enable remote magnetomechanical neural stimulation.ACS Nano14, 8036–8045 (2020)..
Neves, S. R. et al. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks.Cell133, 666–680 (2008)..
Zhao, Y. X. et al. An expanded palette of genetically encoded Ca2+indicators.Science333, 1888–1891 (2011)..
Wang, H. J. et al. Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution.Nat. Commun.15, 5521 (2024)..
Yang, W. J. et al. Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions.eLife7, e32671 (2018)..
Kim, C. K., Adhikari, A.&Deisseroth, K. Integration of optogenetics with complementary methodologies in systems neuroscience.Nat. Rev. Neurosci.18, 222–235 (2017)..
Lenton, I. C. D. et al. Optical tweezers exploring neuroscience.Front. Bioeng. Biotechnol.8, 602797 (2020)..
Wu, T. et al. A photon-driven micromotor can direct nerve fibre growth.Nat. Photonics6, 62–67 (2012)..
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