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Bachmann, J.

Publications and source records attributed to Bachmann, J..

4 recordsLinked to original sources

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↗

Isoform-Level Analysis of 10x Genomics Single-Cell cDNA Libraries from Cultured K562 Cells Using Long-Read Sequencing

Integration of Oxford Nanopore Technologies (ONT) long-read sequencing with 10x Genomics single-cell cDNA libraries enables novel transcript detection, isoform analysis and captures full-length gene body coverage. The purpose of the study was the comparison of three approaches for sequencing 10x Genomics Chromium Single Cell cDNA libraries using long-read sequencing: single-cell full-length transcript sequencing by sampling (FLT-seq), the cDNA-PCR Sequencing Kit (SQK-PCS111) and the PCR Expansion Kit (EXP-PCA001). Our aim was to evaluate their efficiency in enriching full-length cDNA fragments, identifying barcodes, detecting novel isoforms and mutations, and characterizing transcript coverage profiles.

genomics↗

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↗

Mapping atherogenesis mechanisms in smooth muscle cells by targeting genes linked to coronary artery disease

Recent genome-wide association studies (GWAS) have identified multiple vascular cell-expressed genes linked to coronary artery disease (CAD), suggesting that smooth muscle cells (SMCs) and SMC-derived metaplastic cells are promising targets for novel antiatherosclerosis therapies. However, the disease-promoting pathways of most GWAS-identified genes are unknown, hindering their translation into therapeutic targets. This study integrated public GWAS data for CAD and single-cell RNA sequencing (scRNA-seq) analyses of human atherosclerotic plaques to identify 20 GWAS risk genes with a putative mechanism of action in SMCs or SMC-derived cells. Gene perturbation experiments in SMCs coaxed to plaque-relevant phenotypes revealed that the selected risk genes, despite encoding very different types of proteins, regulated shared sets of genes associated with contractile functions, cell cycle pathways, NF{kappa}B, and type I interferon signaling. By integrating information about GWAS gene effect direction and a deep analysis of cholesterol- and stretch-induced gene modules in SMCs, we find evidence that cholesterol-induced signaling is a pro-atherogenic disease mechanism in SMCs that is upregulated by detrimental and downregulated by protective GWAS genes. Overall, our study identifies a set of candidate disease mechanisms in SMCs that are regulated by multiple GWAS genes across several SMC assays. Furthermore, it provides proof-of-concept for using GWAS gene effect directionality to predict the pathogenic effect of candidate disease mechanisms that can be extended to other GWAS genes and cell types in the future.

cell biology↗