Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices

Interfacing neurons with micro- and nano-electronic devices has been a subject of intense study over the last decade. One of the major problems in assembling efficient neuro-electronic hybrid systems is the weak electrical coupling between the components. This is mainly attributed to the fundamental property of living cells to form and maintain an extracellular cleft between the plasma membrane and any substrate to which they adhere. This cleft shunts the current generated by propagating action potentials and thus reduces the signal-to-noise ratio. Reducing the cleft thickness, and thereby increasing the seal resistance formed between the neurons and the sensing surface, is thus a challenge and could improve the electrical coupling coefficient. Using electron microscopic analysis and field potential recordings, we examined here the use of gold micro-structures that mimic dendritic spines in their shape and dimensions to improve the adhesion and electrical coupling between neurons and micro-electronic devices. We found that neurons cultured on a gold-spine matrix, functionalized by a cysteine-terminated peptide with a number of RGD repeats, readily engulf the spines, forming tight apposition. The recorded field potentials of cultured Aplysia neurons are significantly larger using gold-spine electrodes in comparison with flat electrodes.

[1]  U. Wagner,et al.  Focal motility determines the geometry of dendritic spines☆ , 2003, Neuroscience.

[2]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[3]  P. Fromherz,et al.  Fluorescence interference-contrast microscopy of cell adhesion on oxidized silicon , 1997 .

[4]  P. Fromherz,et al.  No correlation of focal contacts and close adhesion by comparing GFP-vinculin and fluorescence interference of DiI , 2001, European Biophysics Journal.

[5]  Daniel Gitler,et al.  Critical calpain‐dependent ultrastructural alterations underlie the transformation of an axonal segment into a growth cone after axotomy of cultured Aplysia neurons , 2003, The Journal of comparative neurology.

[6]  Peter Fromherz,et al.  Field-effect transistor with recombinant potassium channels: fast and slow response by electrical and chemical interactions , 2005 .

[7]  Liguo Wang,et al.  Cryo-EM and single particles. , 2006, Physiology.

[8]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[9]  Peter Fromherz,et al.  FREQUENCY DEPENDENT SIGNAL TRANSFER IN NEURON TRANSISTORS , 1997 .

[10]  S. Grinstein,et al.  Fusion, fission, and secretion during phagocytosis. , 2007, Physiology.

[11]  Armin Lambacher,et al.  Fluorescence interference-contrast microscopy on oxidized silicon using a monomolecular dye layer , 1996 .

[12]  Harvey T. McMahon,et al.  Membrane curvature and mechanisms of dynamic cell membrane remodelling , 2005, Nature.

[13]  Matthias Chiquet,et al.  Electron microscopy of high pressure frozen samples: bridging the gap between cellular ultrastructure and atomic resolution , 2008, Histochemistry and Cell Biology.

[14]  K. Suslick,et al.  Tumor targeting by surface-modified protein microspheres. , 2006, Journal of the American Chemical Society.

[15]  Dieter Braun,et al.  Imaging neuronal seal resistance on silicon chip using fluorescent voltage-sensitive dye. , 2004, Biophysical journal.

[16]  K. Winters,et al.  Novel concepts for improved communication between nerve cells and silicon electronic devices , 2008 .

[17]  M. Spira,et al.  Use of Aplysia neurons for the study of cellular alterations and the resealing of transected axons in vitro , 1996, Journal of Neuroscience Methods.

[18]  Sami Alom Ruiz,et al.  Nanotechnology for Cell–Substrate Interactions , 2006, Annals of Biomedical Engineering.

[19]  2.3: Membrane Curvature , 2022 .

[20]  A. Matus Growth of dendritic spines: a continuing story , 2005, Current Opinion in Neurobiology.

[21]  Kerm Sin Chian,et al.  Adhesion dynamics of porcine esophageal fibroblasts on extracellular matrix protein-functionalized poly(lactic acid). , 2008, Biomedical materials.

[22]  S. Schacher,et al.  Neurite regeneration by Aplysia neurons in dissociated cell culture: modulation by Aplysia hemolymph and the presence of the initial axonal segment , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  Benjamin Geiger,et al.  Molecular engineering of cellular environments: cell adhesion to nano-digital surfaces. , 2007, Methods in cell biology.

[24]  Shlomo Yitzchaik,et al.  Reversible transition of extracellular field potential recordings to intracellular recordings of action potentials generated by neurons grown on transistors. , 2008, Biosensors & bioelectronics.

[25]  P. Fromherz,et al.  The extracellular electrical resistivity in cell adhesion. , 2006, Biophysical journal.

[26]  J. M. Ritchie,et al.  Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[27]  U. Gimsa,et al.  Actin is not required for nanotubular protrusions of primary astrocytes grown on metal nano-lawn , 2007, Molecular membrane biology.

[28]  J. Shappir,et al.  Experimental and theoretical analysis of neuron-transistor hybrid electrical coupling: the relationships between the electro-anatomy of cultured Aplysia neurons and the recorded field potentials. , 2006, Biosensors & bioelectronics.

[29]  W. Almers,et al.  Tetrodotoxin binding to normal depolarized frog muscle and the conductance of a single sodium channel. , 1975, The Journal of physiology.

[30]  M. Spira,et al.  Induction of Growth Cone Formation by Transient and Localized Increases of Intracellular Proteolytic Activity , 1998, The Journal of cell biology.

[31]  J. Shappir,et al.  Electrically conductive 2D-PAN-containing surfaces as a culturing substrate for neurons , 2004, Journal of biomaterials science. Polymer edition.

[32]  Peter Fromherz,et al.  Recombinant maxi-K channels on transistor, a prototype of iono-electronic interfacing , 2001, Nature Biotechnology.

[33]  J. Shappir,et al.  Depletion type floating gate p-channel MOS transistor for recording action potentials generated by cultured neurons. , 2004, Biosensors & bioelectronics.

[34]  Martin Jenkner,et al.  BISTABILITV OF MEMBRANE CONDUCTANCE IN CELL ADHESION OBSERVED IN A NEURON TRANSISTOR , 1997 .

[35]  J. Y. Lim,et al.  Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. , 2007, Tissue engineering.

[36]  Neuroelectronic Interfacing : Semiconductor Chips with Ion Channels , Nerve Cells , and Brain 1 , 2002 .

[37]  Andreas Offenhäusser,et al.  Transmission electron microscopy study of the cell–sensor interface , 2008, Journal of The Royal Society Interface.

[38]  R. A. Ezekowitz,et al.  Phagocytosis: elegant complexity. , 2005, Immunity.