Biology subjects

Schuhmann, F.

Publications and source records attributed to Schuhmann, F..

6 recordsLinked to original sources

bioRxiv2026

3D Printed X-ray Compatible Microfluidics for Online Characterization of Hexosomes: A Synchrotron SAXS-on-Chip Study with Molecular Dynamics Insights

Online structural characterization during microfluidic lipid self-assembly is important for understanding and controlling the formation of nonlamellar liquid crystalline nanodispersions. Here, we report a 3D-printed, X-ray-compatible hydrodynamic flow-focusing microfluidic chip with variable channel dimensions, integrated with synchrotron small-angle X-ray scattering (SAXS), for position-resolved SAXS-on-chip monitoring of Ca2+-triggered hexosome formation. Hexosomes were produced under continuous flow by mixing ethanolic solutions of docosahexaenoic acid monoglyceride (MAG-DHA), the negatively charged phosphatidylglycerol DOPG, and -tocopherol with Ca2+-containing PIPES buffer. Online SAXS-on-chip measurements detected three Bragg reflections characteristic of the internal inverse hexagonal (H2) phase on a tens-of-milliseconds residence-time scale, revealing rapid structural evolution during microfluidic mixing. Complementary ex situ SAXS identified the DOPG/Ca2+ molar ratio as a key parameter modulating the direct vesicle-to-hexosome transformation and the compactness of the internal H2 nanostructures. Dynamic light scattering showed that the flow-rate ratio modulated nanoparticle size, yielding hexosomes with mean hydrodynamic diameters in the range of approximately 120-175 nm and polydispersity index values down to 0.14 at a total flow rate of 200 {micro}L min-1. Cryo-TEM revealed coexistence of hexosomes and vesicular nanostructures, highlighting morphological heterogeneity, while Coarse-Grained Molecular Dynamics simulations supported a central role of Ca2+-DOPG association in promoting a direct lamellar-H2 phase transition. Overall, this work shows that 3D-printed SAXS-compatible microfluidics can integrate continuous production with online structural characterization, providing a basis for future formulation and process optimization of drug-loaded cubosomes, hexosomes, and related nonlamellar liquid crystalline nanodispersions.

biophysics↗

bioRxiv2025

Amyloidogenic proteolysis of APP regulates glutamatergic presynaptic function

Disease causing mutations of Alzheimers disease (AD) point to dysregulations of APP proteolysis. During asymptomatic and early stages of AD, brain recordings revealed hyperexcitation reverting into over-inhibition as dementia progresses. Here, we show that endogenous APP and its proteolytic product APP-CTF{beta}, the precursors of A{beta}, accumulate preferentially at excitatory synapses. Using pharmacological treatments to modulate physiological concentrations of APP-CTF{beta} and A{beta}, we identify APP-CTF{beta} as a key regulator of glutamatergic synaptic transmission. Accumulation of APP-CTF{beta} increases the release probability of synaptic vesicles. Strikingly, monomeric A{beta} counteracts this APP-CTF{beta}-driven hyperexcitability. This suggests that therapeutic strategies clearing monomeric A{beta} could be detrimental during the early hyperexcitability phase of AD.

neuroscience↗

bioRxiv2025

TS2CG as a membrane builder

Molecular dynamics (MD) simulations excel at capturing biological processes at the molecular scale but rely on a well-defined initial structure. As MD simulations now extend to whole-cell-level modeling, new tools are needed to efficiently build initial structures. Here, we introduce TS2CG version 2, designed to construct coarse-grained membrane structures with any desired shape and lateral organization. This version enables precise placement of lipids and proteins based on curvature preference, facilitating the creation of large, near-equilibrium membranes. Additional features include controlled pore generation and the placement of specific lipids at membrane edges for stabilization. Moreover, a Python interface allows users to extend functionality while maintaining the high performance of the C++ core. To demonstrate its capabilities, we showcase challenging simulations, including a Mobius strip membrane, a vesicle with lipid domain as continental plates (Martini globe), and entire mitochondrial membranes exhibiting lipid heterogeneity due to curvature, along with a comprehensive set of tutorials.

biophysics↗

bioRxiv2024

Integrative Molecular Dynamics Simulations Untangle Cross-Linking Data to Unveil Mitochondrial Protein Distributions

Cross-linking mass spectrometry (XL-MS) enables the mapping of protein-protein interactions on the cellular level. When applied to all compartments of mitochondria, the sheer number of cross-links and connections can be over-whelming, rendering simple cluster analyses convoluted and uninformative. To address this limitation, we integrate the XL-MS data, 3D electron microscopy data, and localization annotations with a supra coarse-grained molecular dynamics simulation to sort all data, making clusters more accessible and interpretable. In the context of mitochondria, this method, through a total of 6.9 milliseconds of simulations, successfully identifies known, suggests unknown protein clusters, and reveals the distribution of inner mitochondrial membrane proteins allowing a more precise localization within compartments. Our integrative approach suggests, that two so-far ambigiously placed proteins FAM162A and TMEM126A are localized in the cristae, which is validated through super resolution microscopy. Together, this demonstrates the strong potential of the presented approach. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/612425v2_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@1a3236dorg.highwire.dtl.DTLVardef@16ad120org.highwire.dtl.DTLVardef@1c79bfdorg.highwire.dtl.DTLVardef@1d20e51_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOEntry for the Table of ContentsC_FLOATNO The approach combines cross-linking mass spectrometry, electron microscopy, and coarse-grained molecular dynamics simulations to map protein-protein interactions in mitochondria. This integration makes complex data clusters accessible, revealing protein distributions and localizations. Notably, it allows the localization of FAM162A and TMEM126A through super-resolution microscopy, showcasing the synergy of experimental and computational methods. C_FIG

biophysics↗

bioRxiv2024

The first interneuron of the mouse visual system is tailored to the natural environment through morphology and electrical coupling

The topographic complexity of the mouse retina has long been underestimated, as obvious specializations, like a fovea or visual streak, are absent. However, anatomical and functional gradients exist. It was recently shown that receptive fields of retinal ganglion cells change their shape along the dorso-ventral retinal axis. These variations likely reflect the non-uniform statistics of the visual environment which vary dramatically from ground to sky. Horizontal cells are the first visual interneurons and dictate the synaptic signaling between photoreceptors and bipolar cells by lateral interactions, thereby shaping the receptive fields of down-stream neurons. Thus, we asked whether regional specializations are present at this earliest stage of synaptic circuitry, i.e. at the level of horizontal cells. We analyzed horizontal cell density distributions, morphological properties, localization of gap junction proteins, and the spatial extent of horizontal cell electrical coupling across complete retinas. All of these horizontal cell key features were asymmetrically organized along the dorso-ventral axis. Dorsal horizontal cells were less densely distributed, had larger dendritic trees, and electrical coupling was more extensive than in their ventral counterparts. The steepest change along this gradient occurred at the opsin transition zone of photoreceptors, i.e. the mouse visual horizon. Therefore, our results show that the cellular and synaptic organization of the mouse visual system are adapted to the visual environment at the earliest possible level, and that horizontal cells are well suited to form the cellular substrate for the global gradient previously described for the receptive field structures of retinal ganglion cells.

neuroscience↗

bioRxiv2022

Across atoms to crossing continents: Application of similarity measures to biological location data

Biological processes involve movements across all measurable scales. Similarity measures can be applied to compare and analyze these movements but differ in how differences in movement are aggregated across space and time. The present study reviews frequently-used similarity measures, such as the Hausdorff distance, Frechet distance, Dynamic Time Warping, and Longest Common Subsequence, jointly with several measures less used in biological applications (Wasserstein distance, weak Frechet distance, and Kullback-Leibler divergence), and provides computational tools for each of them that may be used in computational biology. We illustrate the use of the selected similarity measures in diagnosing differences within two extremely contrasting sets of biological data, which, remarkably, may both be relevant for magnetic field perception by migratory birds. Specifically, we assess and discuss cryptochrome protein conformational dynamics and extreme migratory trajectories of songbirds between Alaska and Africa. We highlight how similarity measures contrast regarding computational complexity and discuss those which can be useful in noise elimination or, conversely, are sensitive to spatiotemporal scales.

bioinformatics↗