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  • Review Article
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Nano-bio interfaces for electrical and biochemical signal transduction

Nature Reviews Bioengineering (2025)Cite this article

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Abstract

Nano-bio interfaces are crucial points of interaction between synthetic materials and biological systems at the nanoscale, facilitating the exchange of information and access to biological processes. In this Review, we discuss the design and fabrication of nano-bio interfaces, focusing on the materials, topography and surface chemistry that determine their functionality and the information that can be measured. We highlight the design of nano-bio interfaces for bioelectrical signal detection in heart and brain tissue as well as for biochemical signal transduction across the cell membrane to investigate how cells sense and respond to extracellular environments and physical forces at the nanoscale. Finally, we outline key future milestones in the fabrication and application of nano-bio interfaces, emphasizing the need to overcome technical barriers to provide accessible devices.

Key points

  • Nanofabrication techniques, including top-down and bottom-up approaches, enable the creation of nano-bio interfaces with distinct functionalities.

  • The materials, topography, patterning and surface characteristics of nano-bio interfaces can be precisely engineered to probe diverse biological processes.

  • Nano-bio interfaces provide the capability to measure electrical activity at the cellular, tissue and organ levels.

  • Nano-bio interfaces with designed nanotopography or ligand patterning enable new means to study how cells interact with and respond to their surrounding environment and mechanical stimuli at the molecular scale.

  • Future efforts should focus on overcoming translational barriers and making nano-bio interface devices more accessible.

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Fig. 1: Nano-bio interfaces for probing biological processes.
Fig. 2: Engineering nano-bio interfaces.
Fig. 3: Nano-bio interfaces for electrophysiological recording and modulation.
Fig. 4: Nanotopographical nano-bio interfaces for probing and modulating cellular processes.
Fig. 5: Nano-bio interfaces with 2D ligand patterning for regulation of receptor signalling.

References

  1. Yang, X. et al. Nanotechnology enables novel modalities for neuromodulation. Adv. Mater. 33, 2103208 (2021).

    Article  Google Scholar 

  2. Yang, Y. et al. Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum. Nat. Cell Biol. 26, 1878–1891 (2024).

    Article  Google Scholar 

  3. Jahed, Z. et al. Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes. Nat. Commun. 13, 2253 (2022).

    Article  Google Scholar 

  4. Elnathan, R. et al. Biointerface design for vertical nanoprobes. Nat. Rev. Mater. 7, 953–973 (2022).

    Article  Google Scholar 

  5. Yang, X. et al. Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids. Nat. Biotechnol. 42, 1836–1843 (2024). This article reports kirigami-inspired spiral and honeycomb electronic patterns that can adopt a 3D basket shape when released from the substrate, allowing their integration with neural organoids and assembloids for long-term organoid electrophysiology.

    Article  Google Scholar 

  6. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 16093 (2017).

    Article  Google Scholar 

  7. Higgins, S. G. et al. High-aspect-ratio nanostructured surfaces as biological metamaterials. Adv. Mater. 32, e1903862 (2020).

    Article  Google Scholar 

  8. Jiang, Y. et al. The roles of micro- and nanoscale materials in cell-engineering systems. Adv. Mater. 36, e2410908 (2024).

    Article  Google Scholar 

  9. Coulon, P.-M. et al. Displacement Talbot lithography for nano-engineering of III-nitride materials. Microsyst. Nanoeng. 5, 52 (2019).

    Article  Google Scholar 

  10. Elnathan, R. et al. Maximizing transfection efficiency of vertically aligned silicon nanowire arrays. Adv. Funct. Mater. 25, 7215–7225 (2015).

    Article  Google Scholar 

  11. Harding, F. J. et al. Ordered silicon pillar arrays prepared by electrochemical micromachining: substrates for high-efficiency cell transfection. ACS Appl. Mater. Interfaces 8, 29197–29202 (2016).

    Article  Google Scholar 

  12. Ji, D. et al. Electrospinning of nanofibres. Nat. Rev. Methods Primers 4, 1 (2024).

    Article  Google Scholar 

  13. Gissibl, T., Thiele, S., Herkommer, A. & Giessen, H. Two-photon direct laser writing of ultracompact multi-lens objectives. Nat. Photon. 10, 554–560 (2016).

    Article  Google Scholar 

  14. Geng, Q., Wang, D., Chen, P. & Chen, S.-C. Ultrafast multi-focus 3-D nano-fabrication based on two-photon polymerization. Nat. Commun. 10, 2179 (2019).

    Article  Google Scholar 

  15. Abbott, J., Ye, T., Ham, D. & Park, H. Optimizing nanoelectrode arrays for scalable intracellular electrophysiology. Acc. Chem. Res. 51, 600–608 (2018).

    Article  Google Scholar 

  16. Dipalo, M. et al. Membrane poration mechanisms at the cell-nanostructure interface. Adv. Biosyst. 3, e1900148 (2019).

    Article  Google Scholar 

  17. Fang, Y. et al. Dissecting biological and synthetic soft-hard interfaces for tissue-like systems. Chem. Rev. 122, 5233–5276 (2022).

    Article  Google Scholar 

  18. Li, X. et al. A nanostructure platform for live-cell manipulation of membrane curvature. Nat. Protoc. 14, 1772–1802 (2019).

    Article  Google Scholar 

  19. Sharma, E. et al. Evolution in lithography techniques: microlithography to nanolithography. Nanomaterials 12, 2754 (2022).

    Article  Google Scholar 

  20. Yang, X. et al. Bioinspired neuron-like electronics. Nat. Mater. 18, 510–517 (2019).

    Article  Google Scholar 

  21. Chiappini, C. et al. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nat. Mater. 14, 532–539 (2015).

    Article  Google Scholar 

  22. Leung, C. M. et al. A guide to the organ-on-a-chip. Nat. Rev. Methods Primers 2, 33 (2022).

    Article  Google Scholar 

  23. Pease, A. C. et al. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc. Natl. Acad. Sci. USA 91, 5022–5026 (1994).

    Article  Google Scholar 

  24. Culver, J. C. et al. Three-dimensional biomimetic patterning in hydrogels to guide cellular organization. Adv. Mater. 24, 2344–2348 (2012).

    Article  Google Scholar 

  25. Rodrigo, D. et al. Mid-infrared plasmonic biosensing with graphene. Science 349, 165–168 (2015).

    Article  Google Scholar 

  26. Altug, H., Oh, S.-H., Maier, S. A. & Homola, J. Advances and applications of nanophotonic biosensors. Nat. Nanotechnol. 17, 5–16 (2022).

    Article  Google Scholar 

  27. Abu Hatab, N. A., Oran, J. M. & Sepaniak, M. J. Surface-enhanced Raman spectroscopy substrates created via electron beam lithography and nanotransfer printing. ACS Nano 2, 377–385 (2008).

    Article  Google Scholar 

  28. Garoli, D., Yamazaki, H., Maccaferri, N. & Wanunu, M. Plasmonic nanopores for single-molecule detection and manipulation: toward sequencing applications. Nano Lett. 19, 7553–7562 (2019).

    Article  Google Scholar 

  29. Hanson, L. et al. Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells. Nat. Nanotechnol. 10, 554–562 (2015).

    Article  Google Scholar 

  30. Zhao, W. et al. Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nat. Nanotechnol. 12, 750–756 (2017).

    Article  Google Scholar 

  31. Elfström, N. et al. Surface charge sensitivity of silicon nanowires: size dependence. Nano Lett. 7, 2608–2612 (2007).

    Article  Google Scholar 

  32. Robinson, J. T. et al. Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. Nat. Nanotechnol. 7, 180–184 (2012).

    Article  Google Scholar 

  33. Abbott, J. et al. CMOS nanoelectrode array for all-electrical intracellular electrophysiological imaging. Nat. Nanotechnol. 12, 460–466 (2017). This article demonstrates the application of metal–oxide–semiconductor nanoelectrode arrays for large-scale intracellular recording in cardiac cultures.

    Article  Google Scholar 

  34. Abbott, J. et al. A nanoelectrode array for obtaining intracellular recordings from thousands of connected neurons. Nat. Biomed. Eng. 4, 232–241 (2020).

    Article  Google Scholar 

  35. Chiappini, C. et al. Tutorial: using nanoneedles for intracellular delivery. Nat. Protoc. 16, 4539–4563 (2021).

    Article  Google Scholar 

  36. Buchnev, O. et al. Deep-learning-assisted focused ion beam nanofabrication. Nano Lett. 22, 2734–2739 (2022).

    Article  Google Scholar 

  37. Xie, C., Lin, Z., Hanson, L., Cui, Y. & Cui, B. Intracellular recording of action potentials by nanopillar electroporation. Nat. Nanotechnol. 7, 185–190 (2012).

    Article  Google Scholar 

  38. Cao, Y. et al. Nondestructive nanostraw intracellular sampling for longitudinal cell monitoring. Proc. Natl. Acad. Sci. USA 114, E1866–E1874 (2017).

    Article  Google Scholar 

  39. Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotechnol. 8, 83–94 (2013).

    Article  Google Scholar 

  40. Desbiolles, B. X. E., de Coulon, E., Bertsch, A., Rohr, S. & Renaud, P. Intracellular recording of cardiomyocyte action potentials with nanopatterned volcano-shaped microelectrode arrays. Nano Lett. 19, 6173–6181 (2019).

    Article  Google Scholar 

  41. Xu, A. M. et al. Quantification of nanowire penetration into living cells. Nat. Commun. 5, 3613 (2014).

    Article  Google Scholar 

  42. Lin, Z. C., Xie, C., Osakada, Y., Cui, Y. & Cui, B. Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nat. Commun. 5, 3206 (2014).

    Article  Google Scholar 

  43. Hai, A., Shappir, J. & Spira, M. E. Long-term, multisite, parallel, in-cell recording and stimulation by an array of extracellular microelectrodes. J. Neurophysiol. 104, 559–568 (2010).

    Article  Google Scholar 

  44. Duan, X. et al. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat. Nanotechnol. 7, 174–179 (2012).

    Article  Google Scholar 

  45. Ge, J. et al. Rapid fabrication of complex nanostructures using room-temperature ultrasonic nanoimprinting. Nat. Commun. 12, 3146 (2021).

    Article  Google Scholar 

  46. Shiu, J.-Y., Aires, L., Lin, Z. & Vogel, V. Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat. Cell Biol. 20, 262–271 (2018). This article reports the use of scalable nanoimprint lithography to engineer nanopillar platforms with high spatial resolution for investigating cellular mechanotransduction.

    Article  Google Scholar 

  47. Strale, P.-O. et al. Multiprotein printing by light-induced molecular adsorption. Adv. Mater. 28, 2024–2029 (2016).

    Article  Google Scholar 

  48. von Erlach, T. C. et al. Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate. Nat. Mater. 17, 237–242 (2018).

    Article  Google Scholar 

  49. Lee, S. et al. Simple lithography-free single cell micropatterning using laser-cut stencils. J. Vis. Exp. 158, e60888 (2020).

    Google Scholar 

  50. Gjorevski, N. et al. Tissue geometry drives deterministic organoid patterning. Science 375, eaaw9021 (2022).

    Article  Google Scholar 

  51. Xiang, L. et al. Low-power carbon nanotube-based integrated circuits that can be transferred to biological surfaces. Nat. Electron. 1, 237–245 (2018).

    Article  Google Scholar 

  52. Gao, N. et al. Specific detection of biomolecules in physiological solutions using graphene transistor biosensors. Proc. Natl. Acad. Sci. USA 113, 14633–14638 (2016).

    Article  Google Scholar 

  53. Lee, J. M. et al. The ultra-thin, minimally invasive surface electrode array NeuroWeb for probing neural activity. Nat. Commun. 14, 7088 (2023).

    Article  Google Scholar 

  54. Zhao, S. et al. Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes. Nat. Commun. 11, 1788 (2020).

    Article  Google Scholar 

  55. Yu, L. et al. In-plane epitaxial growth of silicon nanowires and junction formation on Si(100) substrates. Nano Lett. 14, 6469–6474 (2014).

    Article  Google Scholar 

  56. Dillen, D. C., Kim, K., Liu, E.-S. & Tutuc, E. Radial modulation doping in core-shell nanowires. Nat. Nanotechnol. 9, 116–120 (2014).

    Article  Google Scholar 

  57. Qing, Q. et al. Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions. Nat. Nanotechnol. 9, 142–147 (2014).

    Article  Google Scholar 

  58. Zhao, Y. et al. Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording. Nat. Nanotechnol. 14, 783–790 (2019).

    Article  Google Scholar 

  59. Lee, C.-H., Hu, W.-P. & Chen, W.-Y. Electric-field assisted silicon nanowire field effect transistor for the ultra-low concentration nucleic acid detection. Biosens. Bioelectron. 268, 116909 (2025).

    Article  Google Scholar 

  60. Mu, L. et al. Silicon nanowire field-effect transistors — a versatile class of potentiometric nanobiosensors. IEEE Access. 3, 287–302 (2015).

    Article  Google Scholar 

  61. Gao, N. et al. General strategy for biodetection in high ionic strength solutions using transistor-based nanoelectronic sensors. Nano Lett. 15, 2143–2148 (2015).

    Article  Google Scholar 

  62. Lu, L. et al. Soft and MRI compatible neural electrodes from carbon nanotube fibers. Nano Lett. 19, 1577–1586 (2019).

    Article  Google Scholar 

  63. Hong, G., Diao, S., Antaris, A. L. & Dai, H. Carbon nanomaterials for biological imaging and nanomedicinal therapy. Chem. Rev. 115, 10816–10906 (2015).

    Article  Google Scholar 

  64. Demirer, G. S. et al. High aspect ratio nanomaterials enable delivery of functional genetic material without DNA integration in mature plants. Nat. Nanotechnol. 14, 456–464 (2019).

    Article  Google Scholar 

  65. Chen, Z. et al. An integrated logic circuit assembled on a single carbon nanotube. Science 311, 1735–1735 (2006).

    Article  Google Scholar 

  66. Bonaccini Calia, A. et al. Full-bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene microtransistor depth neural probes. Nat. Nanotechnol. 17, 301–309 (2022).

    Article  Google Scholar 

  67. Subedi, S. et al. Multi-material vat photopolymerization 3D printing: a review of mechanisms and applications. NPJ Adv. Manuf. 1, 9 (2024).

    Article  Google Scholar 

  68. O’Halloran, S., Pandit, A., Heise, A. & Kellett, A. Two-photon polymerization: fundamentals, materials, and chemical modification strategies. Adv. Sci. 10, e2204072 (2023).

    Article  Google Scholar 

  69. Ovsianikov, A. et al. Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering. Biomacromolecules 12, 851–858 (2011).

    Article  Google Scholar 

  70. Ovsianikov, A. et al. Laser fabrication of 3D gelatin scaffolds for the generation of bioartificial tissues. Materials 4, 288–299 (2011).

    Article  Google Scholar 

  71. Akolawala, Q. et al. Micro-vessels-like 3D scaffolds for studying the proton radiobiology of glioblastoma-endothelial cells co-culture models. Adv. Healthc. Mater. 13, e2302988 (2024).

    Article  Google Scholar 

  72. Nouri-Goushki, M. et al. 3D printed submicron patterns orchestrate the response of macrophages. Nanoscale 13, 14304–14315 (2021).

    Article  Google Scholar 

  73. Abu Shihada, J. et al. Highly customizable 3D microelectrode arrays for in vitro and in vivo neuronal tissue recordings. Adv. Sci. 11, e2305944 (2024).

    Article  Google Scholar 

  74. Colombo, F. et al. Two-photon laser printing to mechanically stimulate multicellular systems in 3D. Adv. Funct. Mater. 34, 2303601 (2024).

    Article  Google Scholar 

  75. Hinton, T. J. et al. Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci. Adv. 1, e1500758 (2015).

    Article  Google Scholar 

  76. Yang, X. et al. Laminin-coated electronic scaffolds with vascular topography for tracking and promoting the migration of brain cells after injury. Nat. Biomed. Eng. 7, 1282–1292 (2023).

    Article  Google Scholar 

  77. Xue, J., Wu, T., Dai, Y. & Xia, Y. Electrospinning and electrospun nanofibers: methods, materials, and applications. Chem. Rev. 119, 5298–5415 (2019).

    Article  Google Scholar 

  78. Partheniadis, I., Nikolakakis, I., Laidmäe, I. & Heinämäki, J. A mini-review: needleless electrospinning of nanofibers for pharmaceutical and biomedical applications. Processes 8, 673 (2020).

    Article  Google Scholar 

  79. Li, M. et al. Electrospun protein fibers as matrices for tissue engineering. Biomaterials 26, 5999–6008 (2005).

    Article  Google Scholar 

  80. Zhang, X., Baughman, C. B. & Kaplan, D. L. In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth. Biomaterials 29, 2217–2227 (2008).

    Article  Google Scholar 

  81. Baiguera, S. et al. Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering. Biomaterials 35, 1205–1214 (2014).

    Article  Google Scholar 

  82. Tiwari, S. K., Sharma, K., Sharma, V. & Kumar, V. Electrospun Nanofibers: Fabrication, Functionalisation and Applications (Springer Nature, 2021).

  83. Wang, Y., Yokota, T. & Someya, T. Electrospun nanofiber-based soft electronics. NPG Asia Mater. 13, 1–22 (2021).

    Article  Google Scholar 

  84. Buzsáki, G. Large-scale recording of neuronal ensembles. Nat. Neurosci. 7, 446–451 (2004).

    Article  Google Scholar 

  85. Steinmetz, N. A. et al. Neuropixels 2.0: a miniaturized high-density probe for stable, long-term brain recordings. Science 372, eabf4588 (2021).

    Article  Google Scholar 

  86. Liu, J. et al. Syringe-injectable electronics. Nat. Nanotechnol. 10, 629–636 (2015).

    Article  Google Scholar 

  87. Yang, X. et al. Structure deformation and curvature sensing of PIEZO1 in lipid membranes. Nature 604, 377–383 (2022).

    Article  Google Scholar 

  88. Dipalo, M. et al. Plasmonic meta-electrodes allow intracellular recordings at network level on high-density CMOS-multi-electrode arrays. Nat. Nanotechnol. 13, 965–971 (2018).

    Article  Google Scholar 

  89. Sahasrabudhe, A. et al. Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits. Nat. Biotechnol. 42, 892–904 (2024).

    Article  Google Scholar 

  90. Dunlop, J., Bowlby, M., Peri, R., Vasilyev, D. & Arias, R. High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nat. Rev. Drug Discov. 7, 358–368 (2008).

    Article  Google Scholar 

  91. Iachetta, G. et al. Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment. Arch. Toxicol. 97, 509–522 (2023).

    Article  Google Scholar 

  92. Liu, R. et al. High density individually addressable nanowire arrays record intracellular activity from primary rodent and human stem cell derived neurons. Nano Lett. 17, 2757–2764 (2017).

    Article  Google Scholar 

  93. Shokoohimehr, P. et al. High-aspect-ratio nanoelectrodes enable long-term recordings of neuronal signals with subthreshold resolution. Small 18, e2200053 (2022).

    Article  Google Scholar 

  94. Shukla, S. et al. Supra- and sub-threshold intracellular-like recording of 2D and 3D neuronal networks using nanopillar electrode arrays. Microsyst. Nanoeng. 10, 184 (2024).

    Article  Google Scholar 

  95. Dipalo, M. et al. Intracellular and extracellular recording of spontaneous action potentials in mammalian neurons and cardiac cells with 3D plasmonic nanoelectrodes. Nano Lett. 17, 3932–3939 (2017).

    Article  Google Scholar 

  96. Dipalo, M. et al. Intracellular action potential recordings from cardiomyocytes by ultrafast pulsed laser irradiation of fuzzy graphene microelectrodes. Sci. Adv. 7, eabd5175 (2021). This review provides an overview of state-of-the-art technologies for neural recording and modulation.

    Article  Google Scholar 

  97. Desbiolles, B. X. E. et al. Nanovolcano microelectrode arrays: toward long-term on-demand registration of transmembrane action potentials by controlled electroporation. Microsyst. Nanoeng. 6, 67 (2020).

    Article  Google Scholar 

  98. Ojovan, S. M. et al. A feasibility study of multi-site, intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes. Sci. Rep. 5, 14100 (2015).

    Article  Google Scholar 

  99. Dipalo, M. et al. Cells adhering to 3D vertical nanostructures: cell membrane reshaping without stable internalization. Nano Lett. 18, 6100–6105 (2018).

    Article  Google Scholar 

  100. Kyndiah, A. et al. Direct recording of action potentials of cardiomyocytes through solution processed planar electrolyte-gated field-effect transistors. Sens. Actuators B Chem. 393, 134227 (2023).

    Article  Google Scholar 

  101. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010). This article reports a nanoscale FET device that exhibits high pH sensitivity and allows cell penetration for intracellular recordings.

    Article  Google Scholar 

  102. Tian, B. et al. Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nat. Mater. 11, 986–994 (2012).

    Article  Google Scholar 

  103. Floch, P. L. et al. Stretchable mesh nanoelectronics for three-dimensional single-cell chronic electrophysiology from developing brain organoids. Adv. Mater. 34, 2106829 (2022).

    Article  Google Scholar 

  104. Liu, Y. et al. Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation. Nat. Biomed. Eng. 3, 58–68 (2019).

    Article  Google Scholar 

  105. Li, T. L. et al. Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids. Biomaterials 290, 121825 (2022).

    Article  Google Scholar 

  106. Li, C.-H. et al. A highly stretchable autonomous self-healing elastomer. Nat. Chem. 8, 618–624 (2016).

    Article  Google Scholar 

  107. Pașca, S. P. The rise of three-dimensional human brain cultures. Nature 553, 437–445 (2018).

    Article  Google Scholar 

  108. Brassard, J. A., Nikolaev, M., Hübscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22–29 (2021).

    Article  Google Scholar 

  109. Chrisnandy, A., Blondel, D., Rezakhani, S., Broguiere, N. & Lutolf, M. P. Synthetic dynamic hydrogels promote degradation-independent in vitro organogenesis. Nat. Mater. 21, 479–487 (2022).

    Article  Google Scholar 

  110. Lorenzo-Martín, L. F. et al. Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity. Nat. Biotechnol. 43, 727–736 (2025).

    Article  Google Scholar 

  111. Kalmykov, A. et al. Organ-on-e-chip: three-dimensional self-rolled biosensor array for electrical interrogations of human electrogenic spheroids. Sci. Adv. 5, eaax0729 (2019).

    Article  Google Scholar 

  112. Park, Y. et al. Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids. Sci. Adv. 7, eabf9153 (2021).

    Article  Google Scholar 

  113. Fullenkamp, D. E. et al. Simultaneous electromechanical monitoring in engineered heart tissues using a mesoscale framework. Sci. Adv. 10, eado7089 (2024).

    Article  Google Scholar 

  114. Huang, Q. et al. Shell microelectrode arrays (MEAs) for brain organoids. Sci. Adv. 8, eabq5031 (2022).

    Article  Google Scholar 

  115. Martinelli, E. et al. The e-flower: a hydrogel-actuated 3D MEA for brain spheroid electrophysiology. Sci. Adv. 10, eadp8054 (2024).

    Article  Google Scholar 

  116. Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y. & Purcell, E. K. Glial responses to implanted electrodes in the brain. Nat. Biomed. Eng. 1, 862–877 (2017).

    Article  Google Scholar 

  117. Seymour, J. P. & Kipke, D. R. Neural probe design for reduced tissue encapsulation in CNS. Biomaterials 28, 3594–3607 (2007).

    Article  Google Scholar 

  118. Sharon, A., Jankowski, M. M., Shmoel, N., Erez, H. & Spira, M. E. Significantly reduced inflammatory foreign-body-response to neuroimplants and improved recording performance in young compared to adult rats. Acta Biomater. 158, 292–307 (2023).

    Article  Google Scholar 

  119. Hong, G. et al. A method for single-neuron chronic recording from the retina in awake mice. Science 360, 1447–1451 (2018).

    Article  Google Scholar 

  120. Kim, D.-H. et al. Epidermal electronics. Science 333, 838–843 (2011).

    Article  Google Scholar 

  121. Jiang, Y. et al. Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics. Science 375, 1411–1417 (2022).

    Article  Google Scholar 

  122. Zhong, D. et al. High-speed and large-scale intrinsically stretchable integrated circuits. Nature 627, 313–320 (2024).

    Article  Google Scholar 

  123. Liu, Y. et al. Morphing electronics enable neuromodulation in growing tissue. Nat. Biotechnol. 38, 1031–1036 (2020).

    Article  Google Scholar 

  124. Chung, H. U. et al. Binodal, wireless epidermal electronic systems with in-sensor analytics for neonatal intensive care. Science 363, eaau0780 (2019).

    Article  Google Scholar 

  125. Kim, T.-I. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013). This article reports the development of ultrathin, injectable optoelectronic devices, representing a substantial advancement in bioelectronics and optogenetics.

    Article  Google Scholar 

  126. Li, J. et al. A tissue-like neurotransmitter sensor for the brain and gut. Nature 606, 94–101 (2022).

    Article  Google Scholar 

  127. Zhao, C. et al. Implantable aptamer–field-effect transistor neuroprobes for in vivo neurotransmitter monitoring. Sci. Adv. 7, eabj7422 (2021).

    Article  Google Scholar 

  128. Creighton, R. L., Phan, J. & Woodrow, K. A. In situ 3D-patterning of electrospun fibers using two-layer composite materials. Sci. Rep. 10, 7949 (2020).

    Article  Google Scholar 

  129. Cao, Y. et al. Universal intracellular biomolecule delivery with precise dosage control. Sci. Adv. 4, eaat8131 (2018).

    Article  Google Scholar 

  130. Dalby, M. J., Gadegaard, N. & Oreffo, R. O. C. Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. Nat. Mater. 13, 558–569 (2014).

    Article  Google Scholar 

  131. Zhang, M. et al. Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels. Biomaterials 268, 120543 (2021).

    Article  Google Scholar 

  132. Yang, S. et al. Membrane curvature governs the distribution of piezo1 in live cells. Nat. Commun. 13, 7467 (2022).

    Article  Google Scholar 

  133. Chen, Y., Shokouhi, A.-R., Voelcker, N. H. & Elnathan, R. Nanoinjection: a platform for innovation in ex vivo cell engineering. Acc. Chem. Res. 57, 1722–1735 (2024).

    Article  Google Scholar 

  134. Kumar, A. R. K. et al. Non-viral, high throughput genetic engineering of primary immune cells using nanostraw-mediated transfection. Biomaterials 317, 123079 (2025).

    Article  Google Scholar 

  135. Li, D. et al. Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics. Science 349, aab3500 (2015).

    Article  Google Scholar 

  136. Nunez, D. et al. Hotspots organize clathrin-mediated endocytosis by efficient recruitment and retention of nucleating resources. Traffic 12, 1868–1878 (2011).

    Article  Google Scholar 

  137. Willy, N. M. et al. De novo endocytic clathrin coats develop curvature at early stages of their formation. Dev. Cell 56, 3146–3159.e5 (2021).

    Article  Google Scholar 

  138. Cail, R. C., Shirazinejad, C. R. & Drubin, D. G. Induced nanoscale membrane curvature bypasses the essential endocytic function of clathrin. J. Cell Biol. 221, e202109013 (2022). This article demonstrates that induced nanocurvatures can facilitate determination of key proteins involved in curvature evolution in biological processes.

    Article  Google Scholar 

  139. Gopal, S. et al. Porous silicon nanoneedles modulate endocytosis to deliver biological payloads. Adv. Mater. 31, e1806788 (2019).

    Article  Google Scholar 

  140. Moerke, C., Mueller, P. & Nebe, B. Attempted caveolae-mediated phagocytosis of surface-fixed micro-pillars by human osteoblasts. Biomaterials 76, 102–114 (2016).

    Article  Google Scholar 

  141. Yoh, H. Z. et al. The influence of dysfunctional actin on polystyrene-nanotube-mediated mRNA nanoinjection into mammalian cells. Nanoscale 15, 7737–7744 (2023).

    Article  Google Scholar 

  142. Elnathan, R., Tay, A., Voelcker, N. H. & Chiappini, C. The start-ups taking nanoneedles into the clinic. Nat. Nanotechnol. 17, 807–811 (2022).

    Article  Google Scholar 

  143. Shokouhi, A.-R. et al. Engineering efficient CAR-T cells via electroactive nanoinjection. Adv. Mater. 35, e2304122 (2023).

    Article  Google Scholar 

  144. Lou, H.-Y. et al. Membrane curvature underlies actin reorganization in response to nanoscale surface topography. Proc. Natl. Acad. Sci. USA 116, 23143–23151 (2019).

    Article  Google Scholar 

  145. Li, X. et al. Nanoscale surface topography reduces focal adhesions and cell stiffness by enhancing integrin endocytosis. Nano Lett. 21, 8518–8526 (2021).

    Article  Google Scholar 

  146. Anselme, K. & Bigerelle, M. Topography effects of pure titanium substrates on human osteoblast long-term adhesion. Acta Biomater. 1, 211–222 (2005).

    Article  Google Scholar 

  147. Deligianni, D. D. et al. Effect of surface roughness of the titanium alloy Ti-6Al-4V on human bone marrow cell response and on protein adsorption. Biomaterials 22, 1241–1251 (2001).

    Article  Google Scholar 

  148. Zhang, W. et al. Curved adhesions mediate cell attachment to soft matrix fibres in three dimensions. Nat. Cell Biol. 25, 1453–1464 (2023). This article reports the use of nanopillars to reveal a new type of cell adhesion complex, termed ‘curved adhesion’, in response to induced membrane curvatures generated by matrix fibres.

    Article  Google Scholar 

  149. Fischer, R. S. et al. Contractility, focal adhesion orientation, and stress fiber orientation drive cancer cell polarity and migration along wavy ECM substrates. Proc. Natl. Acad. Sci. USA 118, e2021135118 (2021).

    Article  Google Scholar 

  150. Laude, A. J. & Prior, I. A. Plasma membrane microdomains: organization, function and trafficking. Mol. Membr. Biol. 21, 193–205 (2004).

    Article  Google Scholar 

  151. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7, 265–275 (2006).

    Article  Google Scholar 

  152. Lu, C.-H. et al. Membrane curvature regulates the spatial distribution of bulky glycoproteins. Nat. Commun. 13, 3093 (2022).

    Article  Google Scholar 

  153. Shurer, C. R. et al. Physical principles of membrane shape regulation by the glycocalyx. Cell 177, 1757–1770 (2019).

    Article  Google Scholar 

  154. Kockelkoren, G. et al. Molecular mechanism of GPCR spatial organization at the plasma membrane. Nat. Chem. Biol. 20, 142–150 (2024).

    Article  Google Scholar 

  155. Rosholm, K. R. et al. Membrane curvature regulates ligand-specific membrane sorting of GPCRs in living cells. Nat. Chem. Biol. 13, 724–729 (2017).

    Article  Google Scholar 

  156. Yang, C.-Y., Huang, L.-Y., Shen, T.-L. & Yeh, J. A. Cell adhesion, morphology and biochemistry on nano-topographic oxidized silicon surfaces. Eur. Cell. Mater. 20, 415–430 (2010).

    Article  Google Scholar 

  157. Sun, X. et al. Asymmetric nanotopography biases cytoskeletal dynamics and promotes unidirectional cell guidance. Proc. Natl. Acad. Sci. USA 112, 12557–12562 (2015).

    Article  Google Scholar 

  158. Mim, C. & Unger, V. M. Membrane curvature and its generation by BAR proteins. Trends Biochem. Sci. 37, 526–533 (2012).

    Article  Google Scholar 

  159. Ledoux, B. et al. Plasma membrane nanodeformations promote actin polymerization through CIP4/CDC42 recruitment and regulate type II IFN signaling. Sci. Adv. 9, eade1660 (2023).

    Article  Google Scholar 

  160. Brunetti, R. M. et al. WASP integrates substrate topology and cell polarity to guide neutrophil migration. J. Cell Biol. 221, e202104046 (2022). This article reports the use of nanobeads and nanoridges to provide a molecular model of how motile cells interpret the topographical features of their substrate.

    Article  Google Scholar 

  161. Kalukula, Y., Stephens, A. D., Lammerding, J. & Gabriele, S. Mechanics and functional consequences of nuclear deformations. Nat. Rev. Mol. Cell Biol. 23, 583–602 (2022).

    Article  Google Scholar 

  162. Carthew, J. et al. Precision surface microtopography regulates cell fate via changes to actomyosin contractility and nuclear architecture. Adv. Sci. 8, 2003186 (2021).

    Article  Google Scholar 

  163. Zeng, Y. et al. Guiding irregular nuclear morphology on nanopillar arrays for malignancy differentiation in tumor cells. Nano Lett. 22, 7724–7733 (2022).

    Article  Google Scholar 

  164. Seong, H. et al. Size-tunable nanoneedle arrays for influencing stem cell morphology, gene expression, and nuclear membrane curvature. ACS Nano 14, 5371–5381 (2020).

    Article  Google Scholar 

  165. Li, N., Jin, K., Chen, T. & Li, X. A static force model to analyze the nuclear deformation on cell adhesion to vertical nanostructures. Soft Matter 18, 6638–6644 (2022).

    Article  Google Scholar 

  166. Katiyar, A. et al. The nucleus bypasses obstacles by deforming like a drop with surface tension mediated by Lamin A/C. Adv. Sci. 9, e2201248 (2022).

    Article  Google Scholar 

  167. Liang, H. et al. Microtopography-induced nuclear deformation triggers chromatin reorganization and cytoskeleton remodeling. Chem. Biomed. Imaging 2, 481–489 (2024).

    Article  Google Scholar 

  168. Clapham, D. E. Calcium signaling. Cell 80, 259–268 (1995).

    Article  Google Scholar 

  169. Berridge, M. J. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32, 235–249 (2002).

    Article  Google Scholar 

  170. Li, G. et al. Orai1 mediated store-operated calcium entry contributing to MC3T3-E1 differentiation on titanium implant with micro/nano-textured topography. Biomater. Adv. 133, 112644 (2022).

    Article  Google Scholar 

  171. Previdi, A. et al. Nanotopography and microconfinement impact on primary hippocampal astrocyte morphology, cytoskeleton and spontaneous calcium wave signalling. Cells 12, 293 (2023).

    Article  Google Scholar 

  172. Mengqi, S. et al. Micro/nano topography with altered nanotube diameter differentially trigger endoplasmic reticulum stress to mediate bone mesenchymal stem cell osteogenic differentiation. Biomed. Mater. 16, 015024 (2020).

    Article  Google Scholar 

  173. Shi, M. et al. Role of the unfolded protein response in topography-induced osteogenic differentiation in rat bone marrow mesenchymal stem cells. Acta Biomater. 54, 175–185 (2017).

    Article  Google Scholar 

  174. Al-Aghbar, M. A., Jainarayanan, A. K., Dustin, M. L. & Roffler, S. R. The interplay between membrane topology and mechanical forces in regulating T cell receptor activity. Commun. Biol. 5, 40 (2022).

    Article  Google Scholar 

  175. Gawden-Bone, C. et al. Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14. J. Cell Sci. 123, 1427–1437 (2010).

    Article  Google Scholar 

  176. Baranov, M. et al. Podosomes of dendritic cells facilitate antigen sampling. J. Cell Sci. 127, 1052–1064 (2014).

    Google Scholar 

  177. Alapan, Y. & Thomas, S. N. Interfacial T cell engineering. Nat. Rev. Bioeng. 3, 549–564 (2025).

    Article  Google Scholar 

  178. Cai, E. et al. Visualizing dynamic microvillar search and stabilization during ligand detection by T cells. Science 356, eaal3118 (2017).

    Article  Google Scholar 

  179. Aramesh, M. et al. Nanoconfinement of microvilli alters gene expression and boosts T cell activation. Proc. Natl. Acad. Sci. USA 118, e2107535118 (2021). This article introduces a nanopore-based platform for microvilli formation induction in T cells and subsequent T cell activation and expansion, highlighting the potential of nanotopographical strategies for immunotherapy applications.

    Article  Google Scholar 

  180. Wheatley, B. A. et al. Nanotopography modulates cytoskeletal organization and dynamics during T cell activation. Mol. Biol. Cell 33, ar88 (2022).

    Article  Google Scholar 

  181. Tamzalit, F. et al. Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells. Sci. Immunol. 4, eaav5445 (2019).

    Article  Google Scholar 

  182. Ban, M. & Chen, J. Fabrication of plane-type axon guidance substrates by applying diamond-like carbon thin film deposition. Sci. Rep. 13, 8489 (2023).

    Article  Google Scholar 

  183. Amin, H., Dipalo, M., De Angelis, F. & Berdondini, L. Biofunctionalized 3D nanopillar arrays fostering cell guidance and promoting synapse stability and neuronal activity in networks. ACS Appl. Mater. Interfaces 10, 15207–15215 (2018).

    Article  Google Scholar 

  184. Osaki, T. et al. Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons. Nat. Commun. 15, 2945 (2024).

    Article  Google Scholar 

  185. McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K. & Chen, C. S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483–495 (2004).

    Article  Google Scholar 

  186. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  Google Scholar 

  187. Yim, E. K. F., Pang, S. W. & Leong, K. W. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp. Cell Res. 313, 1820–1829 (2007).

    Article  Google Scholar 

  188. Luo, J. et al. The influence of nanotopography on cell behaviour through interactions with the extracellular matrix — a review. Bioact. Mater. 15, 145–159 (2022).

    Google Scholar 

  189. Cao, S. & Yuan, Q. An update of nanotopographical surfaces in modulating stem cell fate: a narrative review. Biomater. Transl. 3, 55–64 (2022).

    Google Scholar 

  190. Qian, W. et al. Nanotopographic regulation of human mesenchymal stem cell osteogenesis. ACS Appl. Mater. Interfaces 9, 41794–41806 (2017).

    Article  Google Scholar 

  191. Wang, X. et al. Discriminating the independent influence of cell adhesion and spreading area on stem cell fate determination using micropatterned surfaces. Sci. Rep. 6, 28708 (2016).

    Article  Google Scholar 

  192. McNamara, L. E. et al. Nanotopographical control of stem cell differentiation. J. Tissue Eng. 2010, 120623 (2010).

    Article  Google Scholar 

  193. Shorten, P. R., McMahon, C. D. & Soboleva, T. K. Insulin transport within skeletal muscle transverse tubule networks. Biophys. J. 93, 3001–3007 (2007).

    Article  Google Scholar 

  194. Engel, J. et al. Shapes, domain organizations and flexibility of laminin and fibronectin, two multifunctional proteins of the extracellular matrix. J. Mol. Biol. 150, 97–120 (1981).

    Article  Google Scholar 

  195. Liu, J. et al. Talin determines the nanoscale architecture of focal adhesions. Proc. Natl. Acad. Sci. USA 112, E4864–E4873 (2015).

    Article  Google Scholar 

  196. Cooper, G. The Cell: A Molecular Approach (Sinauer Associates, Sunderland, MA, 2000).

  197. Cebecauer, M., Spitaler, M., Sergé, A. & Magee, A. I. Signalling complexes and clusters: functional advantages and methodological hurdles. J. Cell Sci. 123, 309–320 (2010).

    Article  Google Scholar 

  198. Zhang, K., Gao, H., Deng, R. & Li, J. Emerging applications of nanotechnology for controlling cell-surface receptor clustering. Angew. Chem. Int. Ed. 58, 4790–4799 (2019).

    Article  Google Scholar 

  199. Arnold, M. et al. Activation of integrin function by nanopatterned adhesive interfaces. Chemphyschem 5, 383–388 (2004). This article reports the design of gold nanodot arrays, manufactured by block-copolymer micelle nanolithography, to control the spatial position of individual receptor–ligand interactions.

    Article  Google Scholar 

  200. Cavalcanti-Adam, E. A. et al. Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys. J. 92, 2964–2974 (2007).

    Article  Google Scholar 

  201. Schvartzman, M. et al. Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level. Nano Lett. 11, 1306–1312 (2011).

    Article  Google Scholar 

  202. Huang, J. et al. Impact of order and disorder in RGD nanopatterns on cell adhesion. Nano Lett. 9, 1111–1116 (2009).

    Article  Google Scholar 

  203. Oria, R. et al. Force loading explains spatial sensing of ligands by cells. Nature 552, 219–224 (2017).

    Article  Google Scholar 

  204. Changede, R., Cai, H., Wind, S. J. & Sheetz, M. P. Integrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions. Nat. Mater. 18, 1366–1375 (2019).

    Article  Google Scholar 

  205. Yu, C.-H. & Groves, J. T. Engineering supported membranes for cell biology. Med. Biol. Eng. Comput. 48, 955–963 (2010).

    Article  Google Scholar 

  206. Groves, J. T., Ulman, N. & Boxer, S. G. Micropatterning fluid lipid bilayers on solid supports. Science 275, 651–653 (1997).

    Article  Google Scholar 

  207. Glazier, R. & Salaita, K. Supported lipid bilayer platforms to probe cell mechanobiology. Biochim. Biophys. Acta Biomembr. 1859, 1465–1482 (2017).

    Article  Google Scholar 

  208. Nair, P. M., Salaita, K., Petit, R. S. & Groves, J. T. Using patterned supported lipid membranes to investigate the role of receptor organization in intercellular signaling. Nat. Protoc. 6, 523–539 (2011).

    Article  Google Scholar 

  209. Salaita, K. et al. Restriction of receptor movement alters cellular response: physical force sensing by EphA2. Science 327, 1380–1385 (2010).

    Article  Google Scholar 

  210. Yu, C.-H. et al. Integrin-matrix clusters form podosome-like adhesions in the absence of traction forces. Cell Rep. 5, 1456–1468 (2013).

    Article  Google Scholar 

  211. Manz, B. N., Jackson, B. L., Petit, R. S., Dustin, M. L. & Groves, J. T-cell triggering thresholds are modulated by the number of antigen within individual T-cell receptor clusters. Proc. Natl. Acad. Sci. USA 108, 9089–9094 (2011). This article reports the design of nanopatterned ligand-modified supported lipid bilayers to control the size of signalling complexes down to the single-molecule level.

    Article  Google Scholar 

  212. Iversen, L. et al. Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics. Science 345, 50–54 (2014).

    Article  Google Scholar 

  213. Huang, W. Y. C. et al. A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS. Science 363, 1098–1103 (2019).

    Article  Google Scholar 

  214. Torres, A. J., Wu, M., Holowka, D. & Baird, B. Nanobiotechnology and cell biology: micro- and nanofabricated surfaces to investigate receptor-mediated signaling. Annu. Rev. Biophys. 37, 265–288 (2008).

    Article  Google Scholar 

  215. Chen, Z. et al. Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility. Proc. Natl. Acad. Sci. USA 115, E5696–E5705 (2018).

    Google Scholar 

  216. Chen, Z., Oh, D., Biswas, K. H., Zaidel-Bar, R. & Groves, J. T. Probing the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility. eLife 10, e67379 (2021).

    Article  Google Scholar 

  217. Oh, D. et al. Competition for shared downstream signaling molecules establishes indirect negative feedback between EGFR and EphA2. Biophys. J. 121, 1897–1908 (2022). This article reports the design of ligand nanopatterns to investigate the interplay between downstream signalling pathways of different receptors.

    Article  Google Scholar 

  218. Freeman, S. A. et al. Integrins form an expanding diffusional barrier that coordinates phagocytosis. Cell 164, 128–140 (2016).

    Article  Google Scholar 

  219. Freeman, S. A. et al. Transmembrane pickets connect cyto- and pericellular skeletons forming barriers to receptor engagement. Cell 172, 305–317 (2018).

    Article  Google Scholar 

  220. Biswas, K. H., Zhongwen, C., Dubey, A. K., Oh, D. & Groves, J. T. Multicomponent supported membrane microarray for monitoring spatially resolved cellular signaling reactions. Adv. Biosyst. 2, 1800015 (2018).

    Article  Google Scholar 

  221. Martínez, E., Engel, E., Planell, J. A. & Samitier, J. Effects of artificial micro- and nano-structured surfaces on cell behaviour. Ann. Anat. 191, 126–135 (2009).

    Article  Google Scholar 

  222. Fajrial, A. K. & Ding, X. Advanced nanostructures for cell membrane poration. Nanotechnology 30, 264002 (2019).

    Article  Google Scholar 

  223. Mouw, J. K., Ou, G. & Weaver, V. M. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 15, 771–785 (2014).

    Article  Google Scholar 

  224. Shin, S. et al. Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy. Nat. Mater. 22, 656–665 (2023).

    Article  Google Scholar 

  225. Ishihara, S. & Haga, H. Matrix stiffness contributes to cancer progression by regulating transcription factors. Cancers 14, 1049 (2022).

    Article  Google Scholar 

  226. Nguyen, T. D. et al. Wafer-scale nanopatterning and translation into high-performance piezoelectric nanowires. Nano Lett. 10, 4595–4599 (2010).

    Article  Google Scholar 

  227. Morton, K. J., Nieberg, G., Bai, S. & Chou, S. Y. Wafer-scale patterning of sub-40 nm diameter and high aspect ratio (>50:1) silicon pillar arrays by nanoimprint and etching. Nanotechnology 19, 345301 (2008).

    Article  Google Scholar 

  228. Cooper, K. Scalable nanomanufacturing — a review. Micromachines 8, 20 (2017).

    Article  Google Scholar 

  229. Huang, Z., Tsui, G. C.-P., Deng, Y. & Tang, C.-Y. Two-photon polymerization nanolithography technology for fabrication of stimulus-responsive micro/nano-structures for biomedical applications. Nanotechnol. Rev. 9, 1118–1136 (2020).

    Article  Google Scholar 

  230. Yang, B., Yu, M. & Yu, H. Azopolymer-based nanoimprint lithography: recent developments in methodology and applications. Chempluschem 85, 2166–2176 (2020).

    Article  Google Scholar 

  231. Liu, R. et al. Ultra-sharp nanowire arrays natively permeate, record, and stimulate intracellular activity in neuronal and cardiac networks. Adv. Funct. Mater. 32, 2108378 (2022).

    Article  Google Scholar 

  232. Rey, B. M. et al. Fully tunable silicon nanowire arrays fabricated by soft nanoparticle templating. Nano Lett. 16, 157–163 (2016).

    Article  Google Scholar 

  233. Chen, Y. et al. Silicon-nanotube-mediated intracellular delivery enables ex vivo gene editing. Adv. Mater. 32, e2000036 (2020).

    Article  Google Scholar 

  234. Elnathan, R., Kantaev, R. & Patolsky, F. Synthesis of hybrid multicomponent disklike nanoparticles. Nano Lett. 8, 3964–3972 (2008).

    Article  Google Scholar 

  235. Xue, J., Xie, J., Liu, W. & Xia, Y. Electrospun nanofibers: new concepts, materials, and applications. Acc. Chem. Res. 50, 1976–1987 (2017).

    Article  Google Scholar 

  236. Choi, Y. S. et al. A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy. Science 376, 1006–1012 (2022).

    Article  Google Scholar 

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Acknowledgements

This work was financially supported by the National Institutes of Health (R35GM141598 to B.C.), a Stanford Big Idea Project on Brain Organogenesis (Wu Tsai Neurosciences Institute) (to B.C. and S.P.P.), and a Wu Tsai Neurosciences Institute Interdisciplinary Postdoctoral Scholar Award (to X.Y.).

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Authors and Affiliations

  1. Department of Chemistry, Stanford University, Stanford, CA, USA

    Xiao Yang, Ching-Ting Tsai, Yang Yang, Wei Zhang, He You, Csaba Forró & Bianxiao Cui

  2. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

    Xiao Yang & Sergiu P. Pașca

  3. Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA

    Xiao Yang, Sergiu P. Pașca & Bianxiao Cui

  4. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Xiao Yang

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Contributions

X.Y. and B.C. conceptualized the manuscript and outlined the initial format. X.Y., C.-T.T., Y.Y., W.Z., H.Y., C.F., S.P.P. and B.C. wrote the manuscript. B.C. supervised the work.

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Correspondence to Bianxiao Cui.

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Yang, X., Tsai, CT., Yang, Y. et al. Nano-bio interfaces for electrical and biochemical signal transduction. Nat Rev Bioeng (2025). https://doi.org/10.1038/s44222-025-00374-7

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