Biology subjects

Offenhaeusser, A.

Publications and source records attributed to Offenhaeusser, A..

5 recordsLinked to original sources

bioRxiv2026

Hierarchical dendrite-inspired organic bioelectronic interfaces for neuronal integration

Brain-machine interfaces rely on intimate electrical communication between living neurons and artificial materials, yet conventional electrode architectures remain structurally different to neuronal tissue, limiting stable cell-electrode coupling and long-term recording. Although conducting polymers and microstructured interfaces have individually improved the electrochemical and biological properties of neural electrodes, integrating neuromimetic architecture with electrically active organic materials to direct neuron-electrode interactions has remained challenging. Here we engineer dendrite-inspired organic microelectrodes by programming the self-assembly of conducting polymer fibers directly on microelectrode arrays. By controlling the electrodeposition process, we generate hierarchical architectures that emulate key stages of dendritic development while preserving the relevant electrochemical properties of conducting polymers. These bioinspired interfaces promote nanoscale membrane conformability, reduce the neuron-electrode cleft, and induce localized membrane engulfment of the electrode structures. The enhanced structural integration is accompanied by increased synaptic protein expression and neuronal excitability within mature primary cortical networks. Furthermore, the dendritic electrodes enable localized laser-assisted optoporation, providing transient intracellular electrophysiological access while maintaining extracellular recording functionality.

neuroscience↗

bioRxiv2026

Single-cell, single-shot stimulation reveals heterogeneous network recruitment not explained by standard functional properties.

Understanding how minimal perturbations influence cortical network dynamics remains a central challenge in neural engineering. While single-cell stimulation has been shown to affect population activity, the resulting variability is often treated as noise rather than an informative feature of network behavior. Here, we investigated how single-cell stimulation reflects heterogeneous modulation of neuronal recruitment and the extent to which these effects can be explained by the functional state of the stimulated cell. For this, we combined single-cell optogenetic stimulation with wide-field calcium imaging in cortical cultures. In each network, a single stimulation event was induced, and subsequent alterations in stimulus-coupled recruitment, synchrony, and pairwise correlations were quantified. Additionally, we evaluated whether the baseline functional state of the stimulated neurons, including their event activity levels and Pearson correlation structures, were linked to the observed network responses. Single cell stimulation induced effects were transient, and the network dynamics recovered over a few seconds within the responder population. Importantly, Our findings demonstrate that the observed direction and magnitude of recruitment changes were not significantly explained by the functional state of the stimulated neurons, indicating that these parameters do not capture the determinants of perturbation-induced network responses. This highlights a possibilities in the future approaches for characterizing network responsiveness and suggests that additional unobserved features govern the response of microcircuits to localized inputs.

neuroscience↗

bioRxiv2024

Flexible 3D kirigami probes for in vitro and in vivo neural applications

Three-dimensional (3D) microelectrode arrays (MEAs) are gaining popularity as brain-machine interfaces and platforms for studying electrophysiological activity. Interactions with neural tissue depend on the electrochemical, mechanical, and spatial features of the recording platform. While planar or protruding two-dimensional MEAs are limited in their ability to capture neural activity across layers, existing 3D platforms still require advancements in manufacturing scalability, spatial resolution, and tissue integration. In this work, we present a customizable, scalable, and straightforward approach to fabricate flexible 3D kirigami MEAs containing both surface and penetrating electrodes, designed to interact with the 3D space of neural tissue. These novel probes feature up to 512 electrodes distributed across 128 shanks in a single flexible device, with shank heights reaching up to 1 mm. We successfully deployed our 3D kirigami MEAs in several neural applications, both in vitro and in vivo, and identified spatially dependent electrophysiological activity patterns. Flexible 3D kirigami MEAs are therefore a powerful tool for large-scale electrical sampling of complex neural tissues while improving tissue integration and offering enhanced capabilities for analyzing neural disorders and disease models where high spatial resolution is required.

neuroscience↗

bioRxiv2019

Correlating surface plasmon resonance microscopy of living and fixated cells with electron microscopy allows for investigation of potential preparation artifacts

AO_SCPLOWBSTRACTC_SCPLOWThe investigation of the cell-substrate interface is of great importance for a broad spectrum of areas such as biomedical engineering, brain-chip interfacing and fundamental research. Due to its unique resolution and the prevalence of instruments, electron microscopy (EM) is used as one of the standard techniques for the analysis of the cell-substrate interface. However, possible artifacts that might be introduced by the required sample preparation have been the subject of speculation for decades. Due to recent advances in Surface plasmon resonance microscopy (SPRM), the technique now offers a label-free alternative for the interface characterization with nanometer resolution in axial direction. In contrast to EM, SPRM studies do not require fixation and can therefore be performed on living cells. Here, we present a workflow that allows us to quantify the impact of chemical fixation on the cell-substrate interface. These measurements confirmed that chemical fixation preserved the average cell-substrate distances in the majority of studied cells. Furthermore, we were able to correlate the SPRM measurements with EM images of the cell-substrate interface of the exact same cells allowing us to identify regions with good agreement between the two methods and reveal artifacts introduced during further sample preparation.

biophysics↗

bioRxiv2017

High Current Optogenetic Channels For Stimulation And Inhibition Of Primary Rat Cortical Neurons

ChR2-XXL and GtACR1 are currently the cation and anion ends of the optogenetic single channel current range. These were used in primary rat cortical neurons in vitro to manipulate neuronal firing patterns. ChR2-XXL provides high cation currents via elevated light sensitivity and a prolonged open state. Stimulating ChR2-XXL expressing putative presynaptic neurons induced neurotransmission. Moreover, stable depolarisation block could be generated in single neurons using ChR2-XXL, proving that ChR2-XXL is a promising candidate for in vivo applications of optogenetics, for example to treat peripheral neuropathic pain. We also addressed an anion channelrhodopsin (GtACR1) for the next generation of optogenetic neuronal inhibition in primary rat cortical neurons. GtACR1 s light-gated chloride conduction was verified in primary neurons and the efficient photoinhibition of action potentials, including spontaneous activity, was shown. Our data also implies that the chloride concentration in neurons decreases during neural development. In both cases, we find surprising applications of these high current channels. For ChR2-XXL inhibition and stimulation are possible, while for GtACR1 the role of Cl-during neural development becomes a new optogenetic target.

molecular biology↗