Biology subjects

Gregurec, D.

Publications and source records attributed to Gregurec, D..

5 recordsLinked to original sources

bioRxiv2026

Electrochemical Deformation of PEDOT:PSS Drives Mechanosensitive Cell Activation

Conducting polymers are widely used in bioelectronic interfaces because of their mixed ionic-electronic conductivity, mechanical compliance, and compatibility with biological systems. However, their electrochemically driven structural dynamics have received little attention as a mechanism for mechanical cell stimulation. Here, we show that electrochemical actuation of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) generates mechanical cues capable of activating endogenous mechanosensitive pathways in HEK293T cells. Transparent PEDOT:PSS films deposited on ITO exhibited a heterogeneous granular morphology and underwent potential-dependent microscopic deformation during electrochemical modulation. Direct optical tracking revealed displacement of the polymer boundary, with structural changes occurring preferentially in polymer-dense regions and propagating toward the film edge. When HEK293T cells were cultured directly on PEDOT:PSS, repeated electrochemical stimulation at -240 mV produced reproducible intracellular Ca2+ responses. Pharmacological inhibition with GsMTx4 attenuated the calcium response, whereas blockade of voltage-gated sodium channels with tetrodotoxin largely preserved it, supporting the involvement of mechanosensitive pathways in the cellular response. These findings identify PEDOT:PSS as an electromechanical biointerface in which electrochemical modulation can introduce a mechanical component alongside the established electrical function of the interface. This mechanical contribution should therefore be considered when interpreting cellular responses to conducting polymer- based electrical stimulation and provides a basis for engineering bioelectronic interfaces that deliberately couple electrical control with mechanotransduction.

bioengineering↗

bioRxiv2025

Remote magnetomechanical neuromodulation uncovers a novel therapeutic mechanism for alleviating Parkinsonian symptoms in freely moving mice

To overcome the limitations of invasive neuromodulation systems, we introduce a wireless magnetomechanical approach for remote, minimally invasive deep brain stimulation (DBS) without chronically implanted electrodes. This method leverages biocompatible nanoscale magnetite nanodiscs (MNDs) with ground vortex magnetisation, which undergo in-plane transitions under low-frequency alternating magnetic fields, thereby generating localised piconewton-scale torques. These torques engage endogenous mechanosensory pathways to modulate neural activity, enabling reversible stimulation without the need for genetic modifications. Calcium imaging validated the rapid neuromodulatory effects of MNDs in vitro and ex vivo, which motivated the subsequent application of magnetomechanical DBS to the subthalamic nucleus in mice. We demonstrated the remote control of motor behaviour in wild-type mice and significant restoration of motor function in a severe hemiparkinsonian model. This study established the first wireless therapeutic magnetomechanical neuromodulation platform that leverages biocompatible nanomaterials and endogenous mechanosensory ion channels, representing a promising step toward untethered, clinically translatable neurotechnology.

neuroscience↗

bioRxiv2025

Biocompatible PVDF Nanofibers with Embedded Magnetite Nanodiscs Enable Wireless Magnetoelectric Neuromodulation

Wireless neuromodulation technologies aim to eliminate the need for invasive hardware and enhance tissue compatibility. Magnetoelectric (ME) materials enable magnetic field-induced electrical stimulation, offering a minimally invasive neural activation. However, conventional ME systems use rigid ceramic components with limited biocompatibility. Here, we report a flexible, predominantly organic ME platform composed of polyvinylidene fluoride (PVDF) nanofibers embedded with anisotropic magnetite nanodiscs (MNDs). These MNDs were selected for their unique ability to exert magnetic torque due to vortex magnetization, and their intrinsic magnetostrictive behaviour. The resulting ME fibers preserve the piezoelectric {beta}-phase of PVDF and exhibit magnetoelectric voltage coefficient of 1.26 Vcm-{superscript 1}Oe-{superscript 1}. We compare two magnetic activation strategies; torque-based and high-frequency magnetostriction, finding that magnetostriction more effectively triggers neuronal responses. In vitro calcium imaging reveals robust activation in primary cortical neurons cultured on ME fibers. Biocompatibility post-stimulation was confirmed on ex vivo human brain tissue, with no increased cell death. Implanted into the premotor cortex of freely moving mice, the fibers enabled wireless modulation of motor behaviour under an alternating magnetic field. This work presents the first demonstration of wireless magnetoelectric neuromodulation using soft, biocompatible fiber composites, paving the way for future bioelectronic interfaces free from rigid components and tethered systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/660052v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@7868e7org.highwire.dtl.DTLVardef@12f32a7org.highwire.dtl.DTLVardef@1a6a7e4org.highwire.dtl.DTLVardef@5876e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Lipolytic and Anti-Adipogenic Effect of Capsaicin, Camphor, and Caffeic acid on Human SGBS Adipocytes

Excess fat accumulation contributes to metabolic disorders such as insulin resistance, type 2 diabetes, cardiovascular disease and increases risk of dementia. Promoting lipolysis and inhibiting adipogenesis through natural compounds offers a promising therapeutic approach to obesity. This study investigates the lipolytic and anti-adipogenic effects of capsaicin, camphor, and caffeic acid in human Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte model. First, we determined appropriate treatment concentrations using MTT assays, which demonstrated a dose dependent reduction in cell viability for all three compounds. Selected doses were applied to differentiating SGBS cells until day 14. Lipid droplet accumulation and free fatty acid release were assessed using Oil Red O (ORO) staining and a lipolysis assay kit, respectively. Gene expression of adipogenic and lipolytic markers was analysed by RT-PCR and TRPV1 receptor involvement was examined by immunofluorescence. A network pharmacology approach incorporating GeneCards, STITCH, and other databases revealed downregulation of PPARG, CEBPA, and FABP4, and upregulation of HSL, ATGL, and PLIN1. TRPV1 activation was prominent in capsaicin treated cells. Network analysis identified shared regulatory hubs such as PPARG, STAT3, and MTOR. All treatments significantly reduced lipid accumulation and increased lipolysis, with capsaicin showing the strongest effects. Combination treatments, especially capsaicin with caffeic acid, exhibited synergistic effects. While the previous studies showed interference of these compounds in the molecular pathways involved in fat cell metabolism, our work establishes for the first time potential thermogenic capacity of camphor individually and of combinatory effects of three compounds to inhibit adipogenesis and promote lipolysis in human adipocytes, potentially through TRPV1 signalling and modulation of metabolic gene networks. These findings highlight their therapeutic potential for metabolic disorders.

cell biology↗

bioRxiv2023

Magnetoelectric Nanodiscs Enable Wireless Transgene-Free Neuromodulation

Deep-brain stimulation (DBS) with implanted electrodes revolutionized treatment of movement disorders and empowered neuroscience studies. Identifying less invasive alternatives to DBS may further extend its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials offers an alternative to invasive DBS. Here, we synthesize magnetoelectric nanodiscs (MENDs) with a core-double shell Fe3O4-CoFe2O4-BaTiO3 architecture with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 {micro}g/mm2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization, which combined with cable theory, corroborates our findings in vitro and informs magnetoelectric stimulation in vivo. MENDs injected into the ventral tegmental area of genetically intact mice at concentrations of 1 mg/mL enable remote control of reward behavior, setting the stage for mechanistic optimization of magnetoelectric neuromodulation and inspiring its future applications in fundamental and translational neuroscience.

bioengineering↗