Biology subjects

Lorenz, C.

Publications and source records attributed to Lorenz, C..

At least 19 recordsLinked to original sources

bioRxiv2026

WhaleSonic: Recordings of cetacean vocal behaviour with hydrophone arrays in Northern Norway

Killer whales, humpback whales, fin whales, and sperm whales converged in a fjord system in Northern Norway during the 2023-2024 winter, where whale watching and fishing vessels add to the acoustic scene. Cetaceans are intensely studied for their acoustic behaviour and communication, and the co-occurrence of four species in confined waters offers a unique opportunity to record them with hydrophone arrays. We present WhaleSonic, a raw acoustic dataset recorded with two synchronised array systems. Four drifting buoys, each carrying a tetrahedral hydrophone array, captured 78 hours of calibrated recordings; seven bottom-mounted hydrophones yielded 52 days of continuous data. Both systems are synchronised to UTC (<1 us and 3-7 ms) and positioned to 2 m accuracy. Transmission experiments and sound velocity measurements provide in-situ ground truth. All data are in physical units and a unified coordinate system, self-documented in HDF5 files, and published with open-source tools. WhaleSonic supports the development of multichannel algorithms for source separation, localisation, sound field analysis, and group communication in free-ranging cetaceans.

animal behavior and cognition↗

bioRxiv2026

Partition Coefficients Reveal Changes in Properties of Low-Contrast Biomolecular Condensates

Biomolecular condensates are domains within cells with distinct compositions, held together by intermolecular cohesion. They are implicated in a variety of cellular processes, and in vitro studies have revealed the molecular driving forces that underly their condensation. However, in vitro condensates do not capture essential features of cellular condensates. In particular, enrichment of proteins, quantified by partition coefficients, is often exaggerated in these simplified systems. We show that the addition of free amino acids and other small molecules to model condensates can bring their partition coefficients within physiological range. In this limit, where there is low biochemical contrast between condensates and their surroundings, we observe striking changes to condensate behavior. Such low-contrast condensates exhibit large fluctuations in shape and composition and show enhanced sensitivity to changes in their environment. These behaviors reflect dramatic shifts to their material properties, including interfacial tension, rheology, and chemical susceptibilities. We note remarkable similarities in these effects across seemingly unrelated two-phase fluid systems. To explain these trends, we reformulate classic models of critical phenomena in terms of partition coefficients. This framework simplifies application of theory to experiments with near-critical fluids and suggests new experimental approaches for assessing condensate physiology in live cells.

biophysics↗

bioRxiv2026

Metabolites Shift Equilibria of Biomolecular Condensates

Biomolecular condensates compartmentalize biochemistry in living cells. While in vitro models of condensates involve only a few components, the cytoplasm is a complex mixture with thousands of components, including many small molecules. While many macromolecular drivers of phase separation have been revealed, the contributions from small molecules have received little attention. To quantify the impact of solutes on biomolecular condensates, we introduce susceptibility, a dimensionless descriptor of condensate response to solute perturbations. We measured how three model condensates, assembled by distinct cohesive mechanisms, respond to diverse solutes including amino acids and nucleotides. Generically, solutes shift condensate phase equilibria, with susceptibilities spanning over four orders of magnitude. These values reflect underlying molecular interactions, consistent with theoretical descriptions including Flory-Huggins and polyphasic linkages. As one example of the predictive power of susceptibility, we exploit enzymatic activity to induce condensation and modulate material properties. Our work establishes susceptibility as an indicator of the sensitivity of biomolecular condensates to solutes, with implications for cell physiology and therapeutic design. SIGNIFICANCE STATEMENTCells compartmentalize biochemistry using biomolecular condensates formed through phase separation. Although cells contain thousands of small molecules, little is known about their influence on condensation. In such complex mixtures, mapping full phase diagrams is infeasible. Alternatively, we introduce susceptibility to characterize system response around a working composition. Using three distinct model condensates and over a dozen solutes, we observe susceptibilities varying over four orders of magnitude. We provide a general thermodynamic framework that clarifies the driving forces behind these responses, rationalizing their magnitude and their dependence on location in the phase diagram. Our work provides a framework for understanding and harnessing solutes to regulate biomolecular condensation, with implications for cell physiology and therapeutic design.

biophysics↗

bioRxiv2025

Structures and zinc ion transport pathways of the human SLC39A family of metal transporters

The SLC39A (ZIP) family of zinc ion transporters play a pivotal role in maintaining zinc homeostasis, which is essential for numerous physiological processes involving enzyme catalysis, protein structure and regulation in signal transduction. This investigation employed AlphaFold3 to predict and analyze the 3D structures of all 14 human ZIP family members and revealed key structural and functional features, including transmembrane domains with eight alpha-helices, extracellular and cytoplasmic domains, dimerization, and zinc ion transport pathways. Unique zinc-binding motifs--composed of histidine, aspartic acid, and glutamic acid--were identified. They facilitate zinc ion attraction, selection, and transport. The findings highlight significant structural diversity in these proteins, with additional alpha-helices, disulfide bonds, and other conserved motifs that together contribute to functional specialization across the ZIP family members. Compared to predictions, which exist only for ZIP4, the models incorporate dimeric structures, rationalize loop conformations, and achieve a higher resolution. The predicted 3D structures offer enhanced insights into zinc ion transport mechanisms and provide a foundation for future research into the structural biology of these proteins and their interacting partners in physiology and pathology.

biochemistry↗

bioRxiv2025

Estimating the motor exploration in reinforcement learning

What motor exploration strategies do animals use to learn a skill from rewards? Reinforcement learning theory provides no guidance for estimating motor exploration -- the behavioral component aimed at discovering better strategies. Inspired by the brains modular organization, we postulate a latent learner that explores via an additive source of ideal randomness it injects into behavior. Assuming the learner is ignorant of other motor components, which is sub-optimal by design, evolutionary fitness argues that these should display mainly non-ideal variability. We test this recipe for behavior decomposition in songbirds subjected to a vocal pitch conditioning task. The explorative component we estimate from vocalizations accounts for the motor contribution of a basal ganglia pathway and the other behavioral component accounts for birds suboptimal learning trajectories. This congruence between normative exploration and brain organization suggests that the evolutionary pressure for behavioral optimality is lesser than to learn from purely random trials.

neuroscience↗

bioRxiv2024

Neural population dynamics during sleep in a songbird vocal circuit resemble sharp wave ripple activity

Similar to motor skill learning in mammals, vocal learning in songbirds requires a set of interconnected brain areas that make up an analogous basal ganglia-thalamocortical circuit known as the anterior forebrain pathway (AFP). Although neural activity in the AFP has been extensively investigated during awake singing, very little is known about its neural activity patterns during other behavioral states. Here, we used chronically implanted Neuropixels probes to investigate spontaneous neural activity in the AFP during natural sleep and awake periods in male zebra finches. We found that during sleep, neuron populations in the pallial region LMAN (lateral magnocellular nucleus of the nidopallium) spontaneously exhibited synchronized bursts that were characterized by a negative sharp deflection in the local field potential (LFP) and a transient increase in gamma power. LMAN population bursts occurred primarily during non-rapid eye movement (NREM) sleep and were highly reminiscent of sharp-wave ripple (SWR) activity observed in rodent hippocampus. We also examined the functional connectivity within the AFP by calculating the pairwise LFP coherence. As expected, delta and theta band coherence within LMAN and Area X was higher during sleep compared to awake periods. Contrary to our expectations, we did not observe strong coherence between LMAN and Area X during sleep, suggesting that the input from LMAN into Area X is spatially restricted. Overall, these results provide the first description of spontaneous neural dynamics within the AFP across behavioral states. Significance statementAlthough cortical and basal ganglia circuits are known to be required for learning in both mammals and birds, little is known about the ongoing spontaneous activity patterns within these circuits, or how they are modulated by behavioral state. Here we prove the first description of cortical-basal ganglia network activity during sleep and awake periods in birds. Within the pallial area LMAN, we observed population-wide bursting events that were highly reminiscent of hippocampal sharp-wave ripple (SWR) activity, suggesting that large-scale population events have diverse functions across vertebrates.

neuroscience↗

bioRxiv2024

Familiarity of an environment prevents song suppression in isolated zebra finches

Despite the wide use of zebra finches as an animal model to study vocal learning and production, little is known about impacts on their welfare caused by routine experimental manipulations such as changing their social context. Here we conduct a post-hoc analysis of singing rate, an indicator of positive welfare, to gain insights into stress caused by social isolation, a common experimental manipulation. We find that isolation in an unfamiliar environment reduces singing rate for several days, indicating the presence of an acute stressor. However, we find no such decrease when social isolation is caused by either removal of a social companion or by transfer to a familiar environment. Furthermore, during repeated brief periods of isolation, singing rate remains high when isolation is induced by removal of social companions, but it fails to recover from a suppressed state when isolation is induced by recurrent transfer to an unknown environment. These findings suggest that stress from social isolation is negligible compared to stress caused by environmental changes and that frequent short visits of an unfamiliar environment are detrimental rather than beneficial. Together, these insights can serve to refine experimental studies and design paradigms maximizing the birds wellbeing and vocal output.

zoology↗

bioRxiv2024

Understanding the binding mechanisms of Alzheimer risk factor TREM2 in lipid bilayer using multi-scale molecular dynamics simulations

Alzheimers disease (AD) is a widespread neurodegenerative condition affecting millions globally. Recent research has implicated variants of the triggering receptor ex-pressed in myeloid cells 2 (TREM2) as risk factors for AD. TREM2, an immunomodula-tory receptor on microglial surfaces, plays a pivotal role in regulating microglial activa-tion by associating with DNAX-activation protein 12 (DAP12). Despite its significance, the mechanism underlying the formation of the complex between the transmembrane domains (TMDs) of TREM2 and DAP12 remains unclear. This study employs multi-scale molecular dynamics (MD) simulations to investigate three TMD complex models, including two derived from experiments and one generated by AlphaFold2. Conducted within a lipid membrane consisting of an 80:20 mixture of phosphatidylcholine (POPC) and cholesterol, our analysis reveals hydrogen bonding interactions between K26 of TREM2 and D16 of DAP12 in all three models, consistent with previous experimen-tal findings. Our results elucidate the different spatial conformations observed in the models and offer insights into the structure of the TREM2/DAP12 TMD complex. Furthermore, we elucidate the role of charged residues in the assembly structure of the complex within the lipid membrane. These findings enhance our understanding of the molecular mechanism governing TREM2/DAP12 complex formation, providing a foundation for designing novel therapeutic strategies to address AD and other neu-rodegenerative diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/584168v2_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@15c1e93org.highwire.dtl.DTLVardef@db697eorg.highwire.dtl.DTLVardef@eb0914org.highwire.dtl.DTLVardef@a12b9a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDifferent TREM2/DAP12 complexes are generated using experimental PDB structures or AlphaFold2 C_LIO_LILong time coarse-grained MD simulations are used for getting the sys-tems stable C_LIO_LIAtomistic detailed complex structures are captured using all-atom sim-ulation C_LIO_LIProvides mechanistic insight into TREM2 transformation from its un-bound state to bounded state C_LIO_LIOffers novel insights into the molecular basis of TREM2/DAP12 sig-nalling pathway C_LI

biophysics↗

bioRxiv2022

Keratin filament mechanics and energy dissipation are determined by metal-like plasticity

Cell mechanics is determined by an intracellular biopolymer network, including intermediate filaments that are expressed in a cell-type specific manner. A prominent pair of intermediate filaments are keratin and vimentin as the epithelial-to-mesenchymal transition is associated with a switch from keratin to vimentin. The transition coincides with a change in cellular mechanics, and thus dynamic properties of the cells. This observation raises the question of how the mechanical properties already differ on the single filament level. Here we use optical tweezers and a computational model to compare the stretching and dissipation behavior of the two filament types. We find that keratin and vimentin filaments behave in opposite ways: keratin filaments elongate, but retain their stiffness, whereas vimentin filaments soften, but retain their length. This finding is explained by fundamentally different ways to dissipate energy: viscous subunits sliding within keratin filaments and non-equilibrium helix unfolding in vimentin filaments.

biophysics↗

bioRxiv2022

Extracting extended vocal units from two neighborhoods in the embedding plane

Annotating and proofreading data sets of complex natural behaviors are tedious tasks because instances of a given behavior need to be correctly segmented from background noise and must be classified with minimal false positive error rate. Low-dimensional embeddings have proven very useful for this task because they provide a visually appealing overview of a data set in which relevant clusters appear spontaneously. However, low-dimensional embeddings introduce errors because they fail to preserve high dimensional distances; and embeddings represent only objects of fixed dimensionality, which conflicts with natural objects such as vocalizations that have variable dimensions stemming from their variable durations. To mitigate these issues, we introduce a semi-supervised method for simultaneous segmentation and clustering of vocalizations. We define vocal units of a given type in terms of two density-based regions in low-dimensional embedding space, one associated with onsets and the other with offsets. We demonstrate our approach on the task of clustering adult zebra finch vocalizations embedded into the 2d plane with UMAP. We show that two-neighborhood (2N) extraction allows the identification of short and long vocal renditions from continuous data streams without initially committing to a particular segmentation of the data. Also, 2N vocal extraction achieves much lower false positive error rate than approaches based on a single defining region.

animal behavior and cognition↗

bioRxiv2022

Phospholipid tail asymmetry allows cellular adaptation to anoxic environments

Membrane biophysical properties are critical to cell fitness and depend on unsaturated phospholipid acyl tails. These can only be produced in aerobic environments since eukaryotic desaturases require molecular oxygen. This raises the question of how cells maintain bilayer properties in anoxic environments. Here, we demonstrate the existence of an alternative pathway to regulate membrane fluidity that exploits phospholipid acyl-tail length asymmetry, replacing unsaturated species in the membrane lipidome. We show that the fission yeast, S. japonicus, which can grow in aerobic and anaerobic conditions, is capable of utilizing this strategy whereas its sister species, the well-known model organism S. pombe, cannot. The incorporation of asymmetric-tailed phospholipids might be a general adaptation to hypoxic environmental niches. One-Sentence SummaryIn anoxic environments, saturated asymmetric acyl-tailed phospholipids can replace unsaturated ones to maintain membrane physical properties.

cell biology↗

bioRxiv2021

Multiscale mechanics and temporal evolution of vimentin intermediate filament networks

The cytoskeleton, an intricate network of protein filaments, motor proteins, and crosslinkers, largely determines the mechanical properties of cells. Among the three filamentous components, F-actin, microtubules, and intermediate filaments (IFs), the IF network is by far the most extensible and resilient to stress. We present a multiscale approach to disentangle the three main contributions to vimentin IF network mechanics - single filament mechanics, filament length, and interactions between filaments - including their temporal evolution. Combining particle tracking, quadruple optical trapping and computational modeling, we derive quantitative information on the strength and kinetics of filament interactions. Specifically, we find that hydrophobic contributions to network mechanics enter mostly via filament elongation kinetics, whereas electrostatics have a direct influence on filament-filament interactions. These results indicate that cells might need to explicitly suppress attractive interactions to re-organize the extremely stable cellular vimentin network.

biophysics↗

bioRxiv2020

Post-Translational Modifications Soften Intermediate Filaments

The mechanical properties of biological cells are determined by the cytoskeleton, a composite biopolymer network consisting of microtubules, actin filaments and intermediate filaments (IFs). By differential expression of cytoskeletal proteins, modulation of the network architecture and interactions between the filaments, cell mechanics may be adapted to varying requirements on the cell. Here, we focus on the intermediate filament protein vimentin and introduce post-translational modifications as an additional, much faster mechanism for mechanical modulation. We study the impact of phosphorylation on filament mechanics by recording force-strain curves using optical traps. Partial phosphorylation softens the filaments. We show that binding of the protein 14-3-3 to phosphorylated vimentin IFs further enhances this effect and speculate that in the cell 14-3-3 may serve to preserve the softening and thereby the altered cell mechanics. We explain our observation by the additional charges introduced during phosphorylation.

biophysics↗

bioRxiv2020

Vimentin Intermediate Filaments Stabilize Dynamic Microtubules by Direct Interactions

The cytoskeleton determines cell mechanics and lies at the heart of important cellular functions. Growing evidence suggests that the manifold tasks of the cytoskeleton rely on the interactions between its filamentous components - actin filaments, intermediate filaments and microtubules. However, the nature of these interactions and their impact on cytoskeletal dynamics are largely unknown. Here, we show in a reconstituted in vitro system that vimentin intermediate filaments stabilize microtubules against depolymerization and support microtubule rescue. To understand these stabilizing effects, we directly measured the interaction forces between individual microtubules and vimentin filaments. Combined with numerical simulations, our observations provide detailed insight into the physical nature of the interactions and how they affect microtubule dynamics. Thus, we describe an additional, direct mechanism for cells to establish the fundamental cross-talk of cytoskeletal components alongside linker proteins. Moreover, we suggest a novel strategy to estimate the binding energy of tubulin dimers within the microtubule lattice.

biophysics↗

bioRxiv2019

Tuning intermediate filament mechanics by indirect and direct charge variations

The cytoskeleton is formed by three types of filamentous proteins - microtubules, actin filaments, and intermediate filaments (IFs) - and enables cells to withstand external and internal forces. Vimentin is the most abundant IF protein in humans and assembles into 10 nm diameter filaments with remarkable mechanical properties, such as high extensibility and stability. It is, however, unclear to which extent these properties are influenced by the electrostatic environment. Here, we study the mechanical properties of single vimentin filaments by employing optical trapping combined with microfluidics. Force-strain curves, recorded at varying ion concentrations and pH values, reveal that the mechanical properties of single vimentin IFs are influenced by pH and ion concentration. By combination with Monte Carlo simulations, we relate these altered mechanics to electrostatic interactions of subunits within the filaments. We thus suggest possible mechanisms that allow cells to locally tune their stiffness without remodeling the entire cytoskeleton.

biophysics↗

bioRxiv2019

In vitro model for resistance in oncogene-dependent tumors at the limit of radiological detectability

In solid tumors, the response to targeted therapy is typically short-lived, as therapy-resistant mutants can quickly expand during therapy. Here we analyze the spectrum of such resistance mutations coexisting in a large population of cancer cells. We use an iterative scheme of artificial evolution to amplify and isolate different resistance mechanisms. As a proof of concept, we apply our scheme to PC-9 cells, a human non-small cell lung cancer cell line with an activating EGFR mutation. The mechanisms we find comprise the well-known gatekeeper-mutation T790M in EGFR, a mutation in NRAS, the amplification of MET-ligand HGF, as well as induction of AKT-mTOR signaling. In this model, a combination of four drugs targeting these mechanisms prevents not only the expansion of resistant cells, but also inhibits the growth of drug-tolerant cells, which can otherwise act as a reservoir for further resistance mutations. These data suggest that a finite number of drugs specifically acting on individual resistant clones may be able to control resistance in oncogenically driven lung cancer.

cancer biology↗

bioRxiv2019

Lateral Subunit Coupling Determines Intermediate Filament Mechanics

The cytoskeleton is a composite network of three types of protein filaments, among which in-termediate filaments (IFs) are the most extensible ones. Two very important IFs are keratin and vimentin, which have similar molecular architectures, but different mechanical behaviors. Here we compare the mechanical response of single keratin and vimentin filaments using optical tweezers. We show that the mechanics of vimentin strongly depends on the ionic strength of the buffer and that its force-strain curve suggests a high degree of cooperativity between subunits. Indeed, a computational model indicates that in contrast to keratin, vimentin is characterized by strong lateral subunit coupling of its charged monomers during unfolding of -helices. We conclude that cells can tune their mechanics by differential use of keratin versus vimentin.

biophysics↗

bioRxiv2019

Nerve Excitability Differences in Slow and Fast Motor Axons of the Rat: more than just Ih

ObjectiveThe objective was to determine if choice of anaesthetic confounded previous conclusions about the differences in nerve excitability indices between fast and slow motor axons.\n\nMethodologyNerve excitability of the rat sciatic nerve was tested while measuring responses of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles. The experiments were conducted with sodium pentobarbital (SP) anaesthetic and compared to previous results that used ketamine-xylazine (KX).\n\nResults and ConclusionsPrevious conclusions about the differences in nerve excitability indices between TA and SOL motor axons using KX were corroborated and extended when experiments were done with SP. Nerve excitability indices sensitive to changes in hyperpolarization-activated inwardly rectifying cation current (Ih) indicated an increase in Ih in SOL axons compared to TA axons (e.g. S3 (-100 %), t=7.949 (df=10), p < 0.0001; TEh (90-100 ms), t=2.659 (df=20), p = 0.0145; hyperpolarizing I/V slope, t=4.308 (df=19), p = 0.0004). SOL axons also had a longer strength-duration time constant (t=3.35 (df=20), p = 0.0032) and a longer and larger magnitude relative refractory period (RRP (ms) t=3.53 (df=12), p = 0.0041; Refractoriness at 2 ms t=0.0055 (df=9), p = 0.0055).\n\nAnaesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischaemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These differences have important implications for the use of nerve excitability measures during processes such as ageing where it is believed that there is a selective loss of fast axons.\n\nNew & NoteworthyNerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of motor axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.

neuroscience↗