Abstract
Coordinated collective electrochemical signals in multicellular assemblies, such as ion fluxes, membrane potentials, electrical gradients, and steady electric fields, play an important role in cell and tissue spatial organization during many physiological processes like wound healing, inflammatory responses, and hormone release. This mass of electric actions cumulates in an en masse activity within cell collectives which cannot be deduced from considerations at the individual cell level. However, continuously sampling en masse collective electrochemical actions of the global electrochemical activity of large-scale electrically coupled cellular assemblies with intracellular resolution over long time periods has been impeded by a lack of appropriate recording techniques. Here we present a bioelectrical interface consisting of low impedance vertical gold nanoelectrode interfaces able to penetrate the cellular membrane in the course of cellular adhesion, thereby allowing en masse recordings of intracellular electrochemical potentials that transverse electrically coupled NRK fibroblast, C2C12 myotube assemblies, and SH-SY5Y neuronal networks of more than 200,000 cells. We found that the intracellular electrical access of the nanoelectrodes correlates with substrate adhesion dynamics and that penetration, stabilization, and sealing of the electrode–cell interface involves recruitment of surrounding focal adhesion complexes and the anchoring of actin bundles, which form a caulking at the electrode base. Intracellular recordings were stable for several days, and monitoring of both basal activity as well as pharmacologically altered electric signals with high signal-to-noise ratios and excellent electrode coupling was performed.
Highlights
T ight cellular assemblies feature dense networks of intercellular contacts and connections that allow electrochemical coupling between cells, for example, gap junctions, chemical synapses, or tunneling nanotubes.[1−3] Electrical signal exchange within these networks is involved in several cellular processes such as myogenic contraction, neuronal information processing, vaso- and lymphendothelia contraction as well as collective cell migration during wound healing.[2,4−6] the exchange of electrical signals enables cellular synchronization and organization.[7]
All values are shown as mean ± s.d. (n = 3 independent experiments). (e) Representative scanning electron microscopy (SEM) image of a normal rat kidney (NRK) cell cultured on a gold nanoelectrode interfaces (gNEIs); the white arrow points to a typical interfacing electrode
We recently reported on the fabrication of gNEIs with vertically aligned, monocrystalline, cigar-shaped nanoelectrodes, which were produced by template-based electrochemical deposition.[25,26]
Summary
T ight cellular assemblies feature dense networks of intercellular contacts and connections that allow electrochemical coupling between cells, for example, gap junctions, chemical synapses, or tunneling nanotubes.[1−3] Electrical signal exchange within these networks is involved in several cellular processes such as myogenic contraction, neuronal information processing, vaso- and lymphendothelia contraction as well as collective cell migration during wound healing.[2,4−6] the exchange of electrical signals enables cellular synchronization and organization (e.g., simultaneous hormone release in pancreatic beta cells).[7]. For en masse electrical activity of electrically coupled cells in the majority of tissues, the whole might be greater and the sum of its parts, meaning that information based on single cell resolution is not necessarily indicative for the en masse action of the cell collective.[10] Conventional glass pipet-based sharp or patch clamp electrode recordings offer excellent electrode-to-membrane coupling coefficients. Extracellular microelectrode arrays have been employed to monitor electrical signals from larger cell culture systems and tissues in vitro and in vivo Such signals only reflect rapid membrane potential changes such as action potentials. These include field-effect transistor-based vertical electrodes with superior electromechanical coupling coefficients, mushroom-shaped gold electrodes for “in cell” recordings, and vertical iridium oxide nanotube electrodes with low impedance.[16−19] All of these interfaces have been successfully employed to record signals
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