Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity
2021; Mary Ann Liebert, Inc.; Volume: 3; Issue: 2 Linguagem: Inglês
10.1089/bioe.2021.0018
ISSN2576-3113
Autores Tópico(s)Planarian Biology and Electrostimulation
ResumoBioelectricityVol. 3, No. 2 Bioelectricity BuzzFree AccessRecent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of BioelectricityAnn M. RajnicekAnn M. RajnicekAnn M. Rajnicek, BS, PhD, FRSB, ,School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom, Media Editor, Bioelectricity E-mail Address: a.m.rajnicek@abdn.ac.ukhttps://orcid.org/0000-0003-2706-0014Search for more papers by this authorPublished Online:16 Jun 2021https://doi.org/10.1089/bioe.2021.0018AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Spring is moving to summer; the birds are singing, the lambs are leaping, and the bioelectricity field is buzzing! This Buzz emphasizes advances in wearable electrical technologies for improving skin wound healing, artificial skin sensors, relief from tinnitus, monitoring pediatric cerebral hydrodynamics, and assessing animal well-being. It also reveals how ion channels control cancer cell metastasis and cold-induced tooth pain, and a role for sodium-glucose co-transporters in taste sensation.A Wee Bug Zapper: A Wearable Nanogenerator to Co-deliver Electrical Stimulation and Antibiotics to Prevent Skin Wound InfectionThis is particularly relevant to this Bioelectricity special issue on Microbial Electrophysiology. Du et al. describe flexible, wearable patches that use electrical stimulation to prevent skin wound bacterial infection and to aid healing.Shuo Du, Nuoya Zhou, Ge Xie, Yu Chen, Huinan Suo, Jiangping Xu, Juan Tao, Lianbin Zhang, Jintao Zhu. Surface-engineered triboelectric nanogenerator patches with drug loading and electrical stimulation capabilities: Toward promoting infected wounds healing. Nano Energy 2021;85:106004.Du et al. have leveraged wearable triboelectric nanogenerator (TENG) technology to configure a miniaturized electrical stimulation device intended to promote healing of cutaneous wounds and prevent bacterial infection. TENGs convert mechanical energy into electricity through the effects of triboelectrification and electrostatic induction, so mechanical body movements can power a wearable electrical stimulation device without an external power source.Bacterial infection is a serious complication for nonhealing wounds and correlates directly with poor outcome. Previous efforts to apply TENGs in an antibacterial context have not overcome key challenges, making small devices that deliver sufficient high-intensity pulsed electric fields (lethal damage to bacterial membranes at >106 V/m) that are also safe for the wearer. Du et al. fabricated a surface-engineered electrode by growing 10 μm thick magnesium-aluminum-layered double hydroxide (LDH) nanosheets on flexible Al foils (LDH@Al). An arch-shaped TENG patch comprising two friction layers was prepared with a lower LDH@Al layer (positive in triboelectric series) and an upper flexible polytetrafluoroethylene polymer substrate (negative in triboelectric series). To demonstrate the output performance of the device an electrode with an area of 49 cm2 was prepared that lit 180 light-emitting diode (LED) lamps when struck with the palm of the hand.To increase the device's antibacterial capacity, a hydrophilic antibiotic (minocycline) was incorporated within the LDH@Al layer (MLDH@Al). When tested in vitro, delivery of 2 V for 24 h using LDH@Al electrodes significantly inhibited growth of Escherichia coli and Staphylococcus aureus bacteria, but identical stimulation parameters using the MLDH@Al electrode doped with 5 μg/mL minocycline almost completely killed both bacterial species. Membrane damage was evident in both species, but S. aureus was more sensitive.In vitro tests demonstrated that electrical stimulation of fibroblast cultures at 1 V (LDH@Al electrodes) doubled cell viability compared with controls, and this increased with voltage, rising to ∼4.5-fold improvement at 8 V. Furthermore, in an in vitro scratch wound assay fibroblast migration was enhanced by 2 V stimulation delivered by LDH@Al at 24 and 48 h compared with controls. Together this suggests a positive influence of electrical stimulation on fibroblast survival and migration, which could aid wound healing.Of importance, the stimulator was then tested in vivo on full thickness wounds in adult mouse skin that were intentionally infected with S. aureus. A miniaturized TENG device was attached over the wound and the mouse's own movements generated AC voltage (0.5–4.5 V) and current (5–40 nA). Ten days after injury the wounds in the group wearing the antibiotic-containing TENG device were healed completely in contrast to those in the control group (wound area ∼31% of original), the group wearing the TENG device not loaded with antibiotic (∼10% original area), the group wearing an (inactive) LDH@Al electrode (∼30% original area), and the antibiotic-loaded (but inactive) MLDH@Al material (∼11% original area). Therefore, the combination of the antibiotic and stimulation delivered by the TENG device was more beneficial than either the antibiotic alone or the electrical stimulation alone.These results offer promise for wearable electrical stimulation devices that free the wearer from the requirement for an external, wired battery pack, provided they prove robust enough to maintain safe levels of stimulation for prolonged periods. Because even small frictional movements between the layers in TENGs (e.g., breathing) can generate electrical output, such devices have the potential for use in bed-bound patients, who are especially susceptible to medically recalcitrant infected pressure ulcers. The ability to dope the material layers with specific drugs provides additional exciting possibilities in the context of personalized medicine for other maladies.Getting a Move on: An Elastin Peptide/Ion Channel Complex Regulates Pancreatic Cancer Cell MigrationPancreatic ductal adenocarcinoma is the most common pancreatic cancer and its highly aggressive nature makes it difficult to treat. Lefebvre et al. have identified a novel membrane protein complex that promotes tumor cell migration and may provide a new therapy target.Thibaut Lefebvre, Pierre Rybarczyk, Clara Bretaudeau, Alison Vanlaeys, Rémi Cousin, Sylvie Brassart-Pasco, Denis Chatelain, Isabelle Dhennin-Duthille, Halima Ouadid-Ahidouch, Bertrand Brassart, Mathieu Gautier. TRPM7/RPSA complex regulates pancreatic cancer cell migration. Front Cell Dev Biol 2020;8:549.Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic cancer. Tissue remodeling in PDAC generates a stromal microenvironment of extracellular matrix components that promotes cell migration and rapid disease progression. Interaction of tumor cell membrane receptors with the extracellular matrix leads to matrix degradation and release of fragments called “matrikines,” including a subtype of elastin-derived peptides (EDPs) called “elastokines.” EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). The Bioelectricity interest relates to the involvement of the transient receptor potential melastatin-related 7 (TRPM7) ion channel in regulating PDAC cell migration and invasion.Using a human pancreatic cancer cell line, Lefebvre et al. demonstrated that the EDPs AG-9 and VG-6 increased cell migration in a Boyden chamber assay. Mechanistically, migration required TRPM7 channel activity because it was impeded in cells transfected with an siRNA targeting TRPM7. Electrophysiological patch clamp recordings showed that AG-9 treatment reversibly stimulated magnesium-inhibited cation currents owing to TRPM7 channel activity. On a tissue level RPSA was expressed strongly in human PDAC tumors, and at the cellular level, immunostaining of TRPM7 and RPSA were colocalized in the human pancreatic cancer cell line, implying formation of a TRPM7/RPSA membrane complex after treatment with AG-9. Collectively, the data suggest that the TRPM7/RPSA complex regulates human pancreatic cancer cell migration.The authors hypothesize that the desmoplastic stroma releases EDPs during pancreatic tumorigenesis, which induces TRPM7/RPSA complex formation in PDAC cells, promoting their migration (therefore, metastasis). This complex may therefore be a promising target for future treatments in PDAC.Have a (M)ice TRP: Transient Receptor Potential Channel Subtype 5 Ion Channel Signaling Underpins Painful Cold Sensation in TeethFor many people biting into something cold can be unpleasant, but the mechanism responsible for that painful sensation has been elusive. Bernal et al. used a novel ex vivo mouse jaw-nerve preparation from transgenic mice to implicate the odontoblast transient receptor potential channel subtype 5 (TRPC5) as the cold sensor in tooth pain.L. Bernal, P. Sotelo-Hitschfeld, C. König, V. Sinica, A. Wyatt, Z. Winter, A. Hein, F. Touska, S. Reinhardt, A. Tragl, R. Kusuda, P. Wartenberg, A. Sclaroff, J. D. Pfeifer, F. Ectors, A. Dahl, M. Freichel, V. Vlachova, S. Brauchi, C. Roza, U. Boehm, D. E. Clapham, J. K. Lennerz, K. Zimmermann. Odontoblast TRPC5 channels signal cold pain in teeth. Sci Adv 2021;7:eabf5567.To carry out its main function of breaking down food the outer layer of each tooth is a hard, mineralized material in contrast to the inner core (pulp), which contains dense networks of blood vessels and nerves that enter through the root. The dentin, a dense calcium matrix comprising most of the tooth volume, sits between the enamel and the pulp. It is laid down and maintained by postmitotic odontoblast cells that reside at the outer margin of the pulp and extend tubular processes into fluid-filled channels in the dentin. Specialized trigeminal nerve ramifications form the “plexus of Raschkow” near the odontoblast cell bodies, extending sensory nerve terminals onto the odontoblast processes within the dentin tubules. This permits the plexus to monitor painful sensations and to regulate inflammatory events.It has been proposed that external thermal or mechanical stimuli can activate sensory nerve endings inside the teeth because the dentinal canals provide a hydraulic link between the stimulus and the nerve endings at the pulp–dentin boundary. But evidence for that model is incomplete. Transient receptor potential (TRP) ion channels are implicated in temperature sensing because some subtypes are activated by cooling and TRPM8 and TRPA1 subtypes act together as temperature sensors in skin. However, acutely isolated human odontoblasts express only TRPM8, not TRPA1, and in rat teeth the roles of TRPM8 and TRPA1 in situ are unclear. The TRPC5 ion channel subtype is present in trigeminal and dorsal root ganglion neurons and is cold sensitive in a heterologous expression system, but whether it is a cold sensor in native cells was not known. Therefore, Bernal et al. explored the roles of TRPA1, TRPM8, and TRPC5 ion channels in cold sensing in teeth.Initial experiments used transgenic TRPC5, TRPA1, and TRPM8 null mice in an inflammatory tooth pain model that exploited a paradoxical increase in sucrose consumption to measure pain. Only in the TRPC5−/− mice was sucrose consumption reversed to the levels of uninjured controls, indicating that TRPC5 channel is relevant to inflammatory pain.For functional examination of the entire tooth sensory system, Bernal et al. developed a novel intact mouse mandible-inferior alveolar nerve (jaw nerve) ex vivo preparation to record action potentials from the inferior alveolar nerve upon cold stimuli. When the intact jaw was exposed to cold, high levels of tooth action potential activity were detected in cold receptors. Adding pharmacological TRPC5 channel blockers to the preparation reduced the cold responses by ∼59% but drugs that modulate TRPM8 had no effect. In jaw-nerve preparations made from TRPC5/A1 double-knockout animals, the cold responses were reduced to 30 Hz) are linked with higher arousal states, theta waves (3–8 Hz) with low arousal, alpha waves (8–12 Hz) with an active awake state, and beta waves (12–30 Hz) with moderate arousal. Assessing the ratio of different wave types generates an EEG power spectrum, with a positive internal state associated with a higher slow wave/fast wave ratio. The power spectrum also provides information about differences in activity of left versus right brain hemispheres. A limitation of EEG recording is that it requires the subject to wear scalp electrodes hard wired to a recording device, and when used in animals they are usually shaved to improve electrode contact, or in some cases invasive electrodes are implanted. These constraints prevent assessment of free moving animals in natural conditions and may influence the result by causing a degree of stress or anxiety.Stomp et al. used a telemetric EEG recording device with five electrodes built into a headband containing a Bluetooth transmitter. The electrodes were positioned using a conductive gel on the (unshaved) forehead over the frontal and parietal bones, with the ground electrode placed behind the ear. There were two cohorts; nine horses housed in typical stables (confined) and nine spending most of their time outdoors (leisure).Horses were found to have individualistic, but consistent EEG profiles over two testing sessions that were not correlated with age or sex. The confined animals showed more right-hemisphere gamma wave activity, which in humans can be associated with anxiety, distraction, or depression. The leisure cohort had more left-hemisphere theta waves, which in humans can be indicative of a calm, attentive mind. However, the pattern of EEG laterality was less reflective of horse welfare than the power spectrum. Horses with indication of welfare alteration (stereotypic behaviors) were characterized by an EEG profile composed mainly of bilateral gamma waves, suggesting a perception bias of the environment. The horses with more theta waves were more positive toward humans, again suggesting a calm, relaxed mindset. Overall, the authors conclude that bilateral and left hemisphere theta activity is a marker of good welfare, whereas bilateral or right hemisphere production of gamma waves alerts potential welfare concern.This study suggests the EEG recordings in free moving animals could be used alongside behavioral observations to reveal their mental state. It might also help to clarify whether brain-wave interpretations from humans translate directly to other species.And that's the current Buzz until next time.FiguresReferencesRelatedDetails Volume 3Issue 2Jun 2021 InformationCopyright 2021, Mary Ann Liebert, Inc., publishersTo cite this article:Ann M. Rajnicek.Recent, Bioelectricity-Related Articles Selected by Ann M. Rajnicek, Media Editor of Bioelectricity.Bioelectricity.Jun 2021.147-153.http://doi.org/10.1089/bioe.2021.0018Published in Volume: 3 Issue 2: June 16, 2021Online Ahead of Print:May 5, 2021PDF download
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