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Membrane Biology (Nano-bio interface)

We delve into the physical properties of cell membranes, including curvature and tension, and their role in regulating crucial intracellular processes at the plasma membrane. Our engineering endeavors focus on nanoscale structures that interface with the cell membrane, affording us unprecedented control over membrane topography. Additionally, we engineer light-activatable and shape-sculpturing proteins to induce membrane curvature through illumination. The ability to control protein activities by light offers unprecedented precision in temporal and spatial dimensions. Through these pioneering efforts, we have uncovered the pivotal roles of membrane curvature and curvature-sensing proteins in integrin adhesion, mechanotransduction, ER-PM contact, endocytosis, and actin dynamics. 

nanobio cell closeup

Selected Publications

  • Zhang W, Lu CH, Nakamoto ML, Tsai CT, Roy AR, Lee CE, Yang Y, Jahed Z, Li X, Cui B*. Curved adhesions mediate cell attachment to soft matrix fibres in three dimensions. Nature Cell Biology, 25, 1453–1464 (2023). [Link] (bioRxiv, 10.1101/2023.03.16.532975. [Link])
  • Lu CH‡, Tsai CT‡, Jones IV T, Chim V, Klausen LH, Zhang W, Li X, Jahed Z*, Cui B*. A NanoCurvS platform for quantitative and multiplex analysis of curvature-sensing proteins. Biomaterials Science, 11, 5205-5217 (2023). [Link]
  • Lu CH, Pedram K, Tsai CT, Jones TE, Li X, Nakamoto M, Bertozzi CR, Cui B*. Membrane curvature regulates the spatial distribution of bulky glycoproteins. Nature Communications, 13, 3093 (2022). [Link]
  • Nakamoto M,  Forró C, Zhang W, Tsai CT, Cui B*. Expansion Microscopy for Imaging the Cell–Material Interface. ACS Nano, 16, 5, 7559–7571 (2022). [Link]
  • Roy AR, Zhang W, Jahed Z, Tsai CT, Cui B, Moerner WE*. Exploring cell surface-nanopillar interactions with 3D super-resolution microscopy. ACS Nano, 16, 1, 192-210 (2022). [Link]
  • Li X‡, Klausen LH‡, Zhang W, Zeinab J, Tsai CT, Li TL, Cui B*. Nanoscale Surface topography reduces focal adhesions and cell stiffness by enhancing integrin endocytosis. Nano Letters, 21, 8518-8526 (2021). [Link]
  • Zhang, W‡, Yang, Y‡, Cui, B*. New perspectives on the roles of nanoscale surface topography in modulating intracellular signaling. Current opinion in solid state & materials science, 25, 100873 (2021). [Link]
  • Li, L., Guo, Q., Lou, H., Liang, J., Yang, Y., Xing, X., Li, H., Han, J., Shen, S., Li, H., Ye, H., Di Wu, H., Cui, B., Wang, S*. Nanobar Array Assay Revealed Complementary Roles of BIN1 Splice Isoforms in Cardiac T-Tubule Morphogenesis. Nano Letters, 20, 6387-6395 (2020). [Link]
  • De Martino S, Zhang W, Klausen L, Lou HY, Li X, Alfonso FA, Cavalli S, Netti PA, Santoro F, Cui B*. Dynamic Manipulation of Cell Membrane Curvature by Light-Driven Reshaping of Azopolymer. Nano Letters, 20, 577-584 (2020). [Link]
  • Lou HY‡, Zhao W‡, Li X, Duan L, Powers A, Akamatsu M, Santoro F, McGuire AF, Cui Y, Drubin DG, Cui B*. Membrane curvature underlies actin reorganization in response to nanoscale surface topography. PNAS, 116, 23143-23151 (2019). [Link]
  • Li X, Matino L, Zhang W, Klausen L, McGuire AF, Lubrano C, Zhao W, Santoro F, Cui B*, A nanostructure platform for live-cell manipulation of membrane curvature. Nature Protocols, 14, 1772-1802 (2019). [Link]
  • Lou HY‡, Zhao W‡, Zeng Y, Cui B*, The Role of Membrane Curvature in Nanoscale Topography-Induced Intracellular Signaling. Accounts of Chemical Research, 51, 1046-1053 (2018). [Link]
  • Dipalo M‡, McGuire AF‡, Lou HY, Caprettini V, Melle G, Bruno G, Lubrano C, Matino L, Li X, De Angelis F*, Cui B*, Santoro F*. Cells Adhering to 3D Vertical Nanostructures: Cell Membrane Reshaping without Stable Internalization. ACS Nano, 18, 6100-6105 (2018). [Link]
  • Santoro F, Zhao W, Joubert LM, Duan L, Schnitker J, van de Burgt Y, Lou HY, Liu B, Salleo A, Cui L, Cui Y, Cui B*, Revealing The Cell-Material Interface With Nanometer Resolution By Focused Ion Beam/Scanning Electron Microscopy. ACS Nano, 11, 8320-8328 (2017). [Link]
  • Zhao W, Hanson L, Lou HY, Akamatsu M, Chowdary PD, Santoro F, Marks JR, Grassart A, Drubin DG*, Cui Y*, Cui B*. Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nature Nanotechnology, 12, 750-756 (2017). [Link]
  • Hanson L, Zhao W, Lou HY, Lin ZL, Lee SW, Chowdary PD, Cui Y*, Cui B*. Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells. Nature Nanotechnology, 10, 554-562 (2015). [Link]
  • Hanson L, Lin ZL, Xie C, Cui Y*, Cui B*. Characterization of the Cell–Nanopillar Interface by Transmission Electron Microscopy. Nano Letters, 12, 5815-5820 (2012). [Link]

Bioelectronics and Optical Electrophysiology

Bioelectric signals are crucial for the physiological functions of rhythmic contraction of cardiomyocytes in the heart and communications of neurons in the brain. We use nanofabrication to develop electronic systems for detecting these small bioelectric signals. Specifically, we are developing vertical nanoelectrodes for scalable and non-invasive intracellular recording of cardiomyocytes. We are also developing mesh electrodes to record from organoids and tissues. We hope to achieve a broad impact by combining the development of new tools with applications to specific biological systems. 

bioelectronics with signal

We are developing a new class of label-free optical electrophysiology for detecting neuroelectric signals. ElectroChromic Optical REcording (ECORE) utilizes the unique property of electrochromic materials that their optical absorption is a function of externally applied voltages. When neurons fire an action potential, the voltage will induce a localize color change of the electrochromic thin film, which allows us to optically read out electrical signals. By detecting reflection instead of fluorescence, ECORE avoids photobleaching and phototoxicity. The ECORE project takes a highly interdisciplinary approach of chemistry (electrochromic chemicals), physics (ultrasensitive optical detection), and biology (neuroscience).

ecore data

Selected Publications for bioelectronics

  • Yang X‡, Forró C‡, Li TL, Miura Y, Zaluska T, Tsai CT, Kanton S, McQueen JP, Chen X, Mollo V, Santoro F, Pașca SP*, Cui B*, Kirigami electronics for long-term electrophysiological recording of human neural organoids and assembloids. Nature Biotechnology, (2024) [Link] (bioRxiv, 10.1101/2023.09.22.559050. [Link])
  • Li TL, Liu Y, Forró C, Yang X, Beker L, Bao Z*, Cui B*, Pașca SP*. Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids. Biomaterials, 290, 121825 (2022). [Link]
  • Yang Y‡, Liu A‡, Tsai CT‡, Liu C, Wu JC, Cui B*. Cardiotoxicity drug screening based on whole-panel intracellular recording. Biosensors Bioelectronics, 216, 114617 (2022). [Link]
  • Jahed Z‡, Yang Y‡, Tsai CT‡, Foster EP, McGuire AF, Yang H, Liu A, Forró C, Yan Z, Jiang X, Zhao MT, Zhang W, Li X, Li T, Pawlosky A, W JC, Cui B*. Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes. Nature Communications, 13, 2253 (2022). [Link]
  • Yang X, McGlynn E, Das R, Pasca SP, Cui B, Heidari H. Nanotechnology enables novel modalities for neuromodulation. Advanced Materials, 33, 2103208 (2021). [Link]
  • Lubrano, C., Matrone, G., Forro, C., Jahed, Z., Offenhaeusser, A., Salleo, A., Cui, B., Santoro, F. Towards biomimetic electronics that emulate cells. MRS Communications, 10, 398-412 (2020). [Link]
  • Liu Y, McGuire AF, Lou HY, Li TL, Tok JB, Cui B*, Bao Z*. Soft Conductive Micropillar Electrode Arrays for Biologically-relevant Electrophysiological Recording. PNAS, 115, 11718-11723 (2018). [Link]
  • McGuire AF, Santoro F, Cui B. Interfacing Cells with Vertical Nanoscale Devices: Applications and Characterization. Annual Review of Analytical Chemistry, 11, 101-126 (2018). [Link]
  • Lin ZC, McGuire AF, Burridge PW, Matsa E, Lou HY, Wu JC, Cui B*. Accurate nanoelectrode recording of human pluripotent stem cell-derived cardiomyocytes for assaying drugs and modeling disease. Microsystems & Nanoengineering, 3,16080 (2017). [Link]
  • Lin ZL, Xie C, Osakada Y, Cui Y*, Cui B*. Iridium Oxide Nanotube Electrodes for Intracellular Measurement of Action Potentials. Nature Communications, 5, 3206 (2014). [Link]
  • Xie C, Lin ZL, Hanson L, Cui Y*, Cui B*. Intracellular recording of action potentials by nanopillar electroporation. Nature Nanotechnology, 7, 185-190 (2012). [Link]

Selected Publications for Optical Electrophysiology

  • Zhou Y, Liu E, Yang Y, Alfonso F, Ahmed B, Nakasone K, Forró C, Müller H*, Cui B*. J. Am. Chem. Soc., 144, 23505-23515 (2022). [Link]
  • Zhou Y, Liu E, Müller H, Cui B*. Optical Electrophysiology: Toward the Goal of Label-Free Voltage Imaging. J. Am. Chem. Soc., 143, 10482-10499 (2021). [Link]
  • Balch HB, McGuire AF, Horng J, Tsai HZ, Qi KK, Duh YS, Forrester PR, Crommie MF, Cui B, Wang F*. Graphene electric field sensor enables single shot label-free imaging of bioelectric potentials. Nano Letter, 21, 4944-4949 (2021). [Link]
  • Alfonso FS, Zhou Y, Liu E, McGuire AF, Yang Y, Kantarci H, Li D, Copenhaver E, Zuchero JB, Müller H*, Cui B*. Label-free optical detection of bioelectric potentials using electrochromic thin films. PNAS, 117, 17260-17268 (2020). [Link]
  • Horng J‡, Balch H‡, McGuire AF, Tsai HZ, Forrester P, Crommie M, Cui B, Wang F*. Imaging electric field dynamics with graphene optoelectronics. Nature Communications, 7, 13704 (2016). [Link]
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