SEARCH · Search bioRxiv

Results for “biophysics”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

bioRxiv2026

Biophysical Characterization of ParBS Condensates suggests a physical mechanism for segregation

The ParABS system orchestrates chromosome segregation in many bacterial species. The centromere-like parS sites serve as nucleation points for the binding of the ParB protein. Subsequent diffusion on adjacent, non-specific DNA regions (spreading) in the presence of CTP and binding of more ParB molecules along with DNA looping via ParB-ParB interactions bring distal parts of the chromosome into proximity. ParB interaction with the ParA-ATPase motor protein, then, drives genomic segregation. It has been shown that in some bacterial species, the ParB-parS complex undergoes phase separation into a condensate. However, the physico-chemical properties of such condensates and their response to forces, such as those they may face in the cell, have not yet been characterized. Performing turbidity measurements in the presence of CTP, various concentrations of DNA and physiological mono and divalent salt, it was shown that Mg2+ facilitates, while K+ concentrations higher than ~20 mM disfavor, condensate formation. Micro rheology measurements showed that condensates of ParB and DNA including parS sites (ParB-parS DNA) in the presence of CTP, are viscoelastic with a viscosity at Troom of ~5 Pa s and able to respond to deformations with a network relaxation time of 0.1 s. Additionally, fluorescence combined with force spectroscopy showed that mechanical disruption of ParB-DNA condensates in the presence of CTP requires 5-7.5 pN of tension in the DNA, which is lower than the force required to stall a molecular motor such as RNA polymerase, but higher than the force required for the relocation of chromosomes and plasmids during segregation. These results support the idea that ParB-parS condensates dynamically rearrange at the molecular level while maintaining the cohesion necessary to sustain the drag force of segregation without interfering with genomic transactions. This physical mechanism could be the basis for the critical role of ParB-parS condensates in organizing and partitioning bacterial chromosomes.

biophysics↗

bioRxiv2026

Edge-Aware Graph Attention Networks for Interpreting Biophysical Mechanisms from Molecular Dynamics Simulations

Graph attention networks (GATs) are emerging as powerful aritficial intelligence (AI) tools for learning biomolecular dynamics, yet extracting mechanistic insight from learned attention remains challenging. Here, we present an interpretable AI approach that combines molecular dynamics prediction with mechanistic interpretation through attention-derived communication networks. We develop three edge-aware GAT models - Edge-Conditioned, Edge-Injected, and Edge-Gated - that differ in how edge information is incorporated during message passing. Relative to a standard GAT, our edge-aware models improve coordinate prediction while recovering complementary aspects of residue communication. Application to Chignolin and HIV-1 protease demonstrates their ability to characterize communication networks underlying protein folding, allostery, and mutation-induced functional remodeling. Analysis of the communication networks using graph-based descriptors of communication throughput, intensity, and relay revealed that the Edge-Conditioned model preferentially emphasizes communication hubs characterized by high communication throughput and intensity, the Edge-Injected model preferentially highlights high-intensity communication within functionally important regions, and the Edge-Gated model most clearly resolves long-range communication relay. Overall, this approach provides an interpretable AI strategy for uncovering the communication mechanisms that underlie folding, allostery, and long-range signal propagation in molecular machines, while also supporting AI-guided modulation of biomolecular function and rational protein engineering.

biophysics↗

bioRxiv2026

Digital molecular kinetics enabled by large-scale nanopore arrays for multidimensional biophysical profiling

While widely used, traditional technologies like surface plasmon resonance (SPR) are limited by narrow temporal windows (transient capture and baseline drift), dynamic heterogeneity, and poor physiological temperature performance. Meanwhile, early nanopore approaches are often constrained by limited throughput and heavy reliance on customized modification schemes. Here, we present a digital molecular kinetics (DMK) platform based on large-scale nanopore arrays. By introducing a universal coupling and probe reporting system, DMK achieves broad versatility across diverse molecular pairs, including proteins, peptides, small molecules, DNA, and polymerase complexes. In addition to accurately recovering classical SPR association and dissociation rate constants, by harnessing massive single-molecule event analysis, DMK breaks traditional performance boundaries: it facilitates robust thermodynamic-kinetic profiling across a wide temperature range, resolves distinct conformations in heterogeneous samples, enables ultra-low dissociation rate quantification via maximum likelihood estimation, and reveals energy wells via voltage gradients for binding analysis against environmental perturbations. Furthermore, DMK enables the capture of rapid binding events missed by SPR, offering a new perspective on molecular interaction complexity. This platform offers an effective alternative and upgrade to SPR, opening a digital paradigm for complex molecular analysis and drug discovery.

biophysics↗

bioRxiv2016

Floral Radiometry: A Biophysical Basis to Characterize Landscapes.

This paper presents early results on studies of floral spectral reflectance of angiosperms and introduces floral radiometry as an emergent dimension of ecological research in India. Floral spectral reflectance of 121 angiosperm species was measured using hand-held spectroradiometer. The authors describe spectral reflectance of seven representative species within 350-800 nanometer region of the electromagnetic spectrum. Characteristic absorption and reflection of flowers, in ultraviolet and visible regions of the spectrum is reported. Near infrared reflectance was consistently high for all species studied. Flower color is unique to a species and importance of understanding flower color from pollinators perspective is highlighted.

ecology↗

bioRxiv2016

Relationships between chromosomal aberration breakpoints and chromosomal contacts: biophysical modeling study

Radiation-induced chromosomal exchange aberrations (CAs) are formed presumably at contacts of damaged chromosomal loci. For sparsely ionizing radiation, distribution of aberrations along the chromosome should depend on distribution of contacts, i.e. on 3D organization of the chromosome. The progress in experimental techniques for study of chromosomal contacts and for precise localization of aberration breakpoints allows to verify contacts-based mechanisms of CA formation experimentally. In the present work, the polymer model of mouse interphase chromosome 18 is developed. On this basis the experimental data on contacts and aberrations are jointly analyzed. We demonstrate high correlation between chromosomal contacts and aberrations breakpoint distributions. Possible factors and alternative mechanisms which could modify breakpoint distributions are discussed.

cancer biology↗

bioRxiv2020

INFLUENCE OF ENERGY DEFICIENCY ON THE MOLECULAR PROCESSES OF SUBSTANTIA NIGRA PARS COMPACTA CELL FOR UNDERSTANDING PARKINSONIAN NEURODEGENERATION: A COMPREHENSIVE BIOPHYSICAL COMPUTATIONAL MODEL

Parkinsons disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that "Energy deficiency at a sub-cellular/cellular/systems level can be a common underlying cause for SNc cell loss in PD." Here, we propose a comprehensive computational model of SNc cell which helps us to understand the pathophysiology of neurodegeneration at subcellular level in PD. The proposed model incorporates a rich vein of molecular dynamics related to SNc neurons such as ion channels, active pumps, ion exchangers, dopamine turnover processes, energy metabolism pathways, calcium buffering mechanisms, alpha-synuclein aggregation, Lewy body formation, reactive oxygen species (ROS) production, levodopa uptake, and apoptotic pathways. The proposed model was developed and calibrated based on experimental data. The influx of glucose and oxygen into the model was controlled, and the consequential ATP variations were observed. Apart from this, the dynamics of other molecular players (alpha-synuclein, ROS, calcium, and dopamine) known to play an important role in PD pathogenesis are also studied. The aim of the study was to see how deficits in supply of energy substrates (glucose and oxygen) lead to a deficit in ATP, and furthermore, deficits in ATP are the common factor underlying the pathological molecular-level changes including alpha-synuclein aggregation, ROS formation, calcium elevation, and dopamine dysfunction. The model suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modelling framework to understand the neurodegenerative processes underlying PD.

neuroscience↗

bioRxiv2020

Biophysical forces rewire cell metabolism to guide microtubule-dependent cell mechanics

Mechanical signals regulate cell shape and influence cell metabolism and behavior. Cells withstand external forces by adjusting the stiffness of its cytoskeleton. Microtubules (MTs) act as compression-bearing elements in response to mechanical cues. Therefore, MT dynamics affect cell mechanics. Yet, how mechanical loads control MT dynamics to adjust cell mechanics to its locally constrained environment has remained unclear. Here, we show that mechanical forces rewire glutamine metabolism to promote MT glutamylation and force cell mechanics, thereby modulating mechanodependent cell functions. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, depletion of the tubulin glutamylase TTLL4 or overexpression of tubulin mutants lacking glutamylation site(s) increased MT dynamics, cell compliance and contractility, and thereby impacted cell spreading, proliferation and migration. Together our results indicate that mechanical cues sustain cell mechanics through glutaminolysis-dependent MT glutamylation, linking cell metabolism to MT dynamics and cell mechanics. Furthermore, our results decipher part of the enigmatic tubulin code that coordinates the fine tunable properties of MT mechanics, allowing cells to adjust the stiffness of their cytoskeleton to the mechanical loads of their environment.

cell biology↗

bioRxiv2020

A biophysical and structural analysis of DNA binding by oligomeric hSSB1 (NABP2/OBFC2B)

The oxidative modification of DNA can result in the loss of genome integrity and must be repaired to maintain overall genomic stability. We have recently demonstrated that human single stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) plays a crucial role in the removal of 8-oxo-7,8-dihydro- guanine (8-oxoG), the most common form of oxidative DNA damage. The ability of hSSB1 to form disulphide-bonded tetramers and higher oligomers in an oxidative environment is critical for this process. In this study, we have used nuclear magnetic resonance (NMR) spectroscopy and surface plasmon resonance (SPR) experiments to determine the molecular details of ssDNA binding by oligomeric hSSB1. We reveal that hSSB1 oligomers interact with single DNA strands containing damaged DNA bases; however, our data also show that oxidised bases are recognised in the same manner as undamaged DNA bases. We further demonstrate that oxidised hSSB1 interacts with ssDNA with a significantly higher affinity than its monomeric form confirming that oligomeric proteins such as tetramers can bind directly to ssDNA. NMR experiments provide evidence that oligomeric hSSB1 is able to bind longer ssDNA in both binding polarities using a distinct set of residues different to those of the related SSB from Escherichia coli.

biochemistry↗

bioRxiv2020

Reef Cover: a coral reef classification for global habitat mapping from biophysical remote sensing.

Coral reef management and conservation stand to benefit from improved high-resolution global mapping. Yet classifications employed in large-scale reef mapping to date are typically poorly defined, not shared or region-specific. Here we present Reef Cover, a new coral reef geomorphic zone classification, developed to support global-scale coral reef habitat mapping in a transparent and version-based framework. We developed scalable classes by focusing on attributes that can be observed remotely, but whose membership rules also reflect knowledge of reef formation, growth and functioning. Bridging the divide between earth observation data and geo-ecological knowledge of reefs, Reef Cover maximises the trade-off between applicability at global scales, and relevance and accuracy at local scales. We use the Caroline and Mariana Island chains in the Pacific as a case study to demonstrate use of the classification scheme and its scientific and conservation applications. The primary application of Reef Cover is the Allen Coral Atlas global coral reef mapping project, but the system will support bespoke reef mapping conducted at a variety of spatial scales.

systems biology↗

bioRxiv2020

Cytoplasm Biophysical Properties Madolute Microtubule Dynamics

The cytoplasm is a crowded, visco-elastic environment whose physical properties change according to physiological or developmental states. How the physical properties of the cytoplasm impact cellular functions in vivo remain poorly understood. Here, we probed the effects of cytoplasmic concentration on microtubules by applying osmotic shifts to fission yeast, moss, and mammalian cells. We show that both the rates of microtubule polymerization and depolymerization scale linearly and inversely with cytoplasmic concentration; an increase in cytoplasmic concentration decreases the rates of microtubule polymerization and depolymerization proportionally, while a decrease in cytoplasmic concentration leads to the opposite. Numerous lines of evidence indicate that these effects are due to changes in cytoplasmic viscosity rather than cellular stress responses or macromolecular crowding per se. We reconstituted these effects on microtubules in vitro by tuning viscosity. Our findings indicate that, even in normal conditions, the viscosity of cytoplasm modulates the reactions underlying microtubule dynamic behaviors.

cell biology↗

bioRxiv2021

Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53

Cellular senescence is protective against external oncogenic stress, but its accumulation causes aging-related diseases. Forkhead box O4 (FOXO4) and p53 are human transcription factors known to promote senescence by interacting each other and activating p21 transcription. Inhibition of the interaction is a strategy for inducing apoptosis of senescent cells, but the binding surfaces that mediate the FOXO4-p53 interaction remain elusive. Here, we investigated two binding sites involved in the interaction between FOXO4 and p53 by NMR spectroscopy. NMR chemical shift perturbation analysis showed that the binding between FOXO4s forkhead domain (FHD) and p53s transactivation domain (TAD), and between FOXO4s C-terminal transactivation domain (CR3) and p53s DNA binding domain (DBD), mediate the FOXO4-p53 interaction. Isothermal titration calorimetry data showed that both interactions have micromolar Kd values, and FOXO4 FHD-p53 TAD interaction has a higher binding affinity. Also, we showed that the FOXO4 CR3-binding surface of FOXO4 FHD interacts with p53 TAD2, and FOXO4 CR3 interacts with the DNA/p53 TAD-binding surface of p53 DBD, suggesting a network of potentially competitive and/or coordinated interactions. Based on the results, we propose that the dual interaction contributes to two TFs proper location on the p21 promoter site and consequently promotes p21 transcription and cell senescence. This work provides structural information at the molecular level that is key to understanding the interplay of two proteins responsible for cellular senescence. Conflicts of interestNone

biochemistry↗

bioRxiv2021

Biophysical and proteomic analyses suggest functions of Pseudomonas syringae pv tomato DC3000 extracellular vesicles in bacterial growth during plant infection

Vesiculation is a process employed by Gram-negative bacteria to release extracellular vesicles (EVs) into the environment. Bacterial EVs contain molecular cargo from the donor bacterium and play important roles in bacterial survival and growth. Here, we describe EV production in plant-pathogenic Pseudomonas syringae pv. tomato DC3000 (Pto DC3000), the causal agent of bacterial speck disease. Cultured Pto DC3000 exhibited EV structures both on the cell surface and in the vicinity of bacterial cells, observed as outer membrane vesicle (OMV) release. We used in-solution trypsin digestion coupled to mass spectrometry to identify 369 proteins enriched in EVs recovered from cultured Pto DC3000. The predicted localization profile of EV proteins supports the production of EVs also in the form of outer-inner-membrane vesicles (OIMVs). EV production varied slightly between bacterial lifestyles and also occurred in planta. The potential contribution of EVs to Pto DC3000 plant infection was assessed using plant treatments and bioinformatic analysis of the EV-enriched proteins. While these results identify immunogenic activities of the EVs, they also point at roles for EVs in bacterial defences and nutrient acquisition by Pto DC3000.

plant biology↗

bioRxiv2021

Biophysical demonstration of co-packaging of glutamate and GABA in individual synaptic vesicles in the central nervous system

Many mammalian neurons release multiple neurotransmitters to activate diverse classes of ionotropic receptors on their postsynaptic targets. Entopeduncular nucleus somatostatin (EP Sst+) neurons that project to the lateral habenula (LHb) release both glutamate and GABA, but it is unclear if these are packaged into the same or segregated pools of synaptic vesicles. Here we describe a novel method combining electrophysiology, spatially-patterned optogenetics, and computational modeling designed to analyze the mechanism of glutamate/GABA corelease. We find that the properties of PSCs elicited in LHb neurons by optogenetic activation of EP Sst+ terminals are only consistent with co-packaging of glutamate and GABA into individual vesicles. Furthermore, serotonin, which acts presynaptically to weaken EP Sst+ to LHb synapses, does so by altering the release probability of vesicles containing both transmitters. Our approach is broadly applicable to the study of multi-transmitter neurons throughout the brain and our results constrain mechanisms of neuromodulation in LHb.

neuroscience↗

bioRxiv2021

Cross-frequency slow oscillation-spindle coupling in a biophysically realistic thalamocortical neural mass model

Sleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often timelock and are implicated in the memory formation. Here, we analyze a neural mass model of the thalamocortical loop of which the cortical node can generate slow oscillations (approx. 1 Hz) while its thalamic component can generate fast sleep spindles of{sigma} -band activity (12-15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic nodes potassium leak and anomalous rectifying currents, and for different parameter regimes of the cortical node. The latter are: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced{sigma} -band activity in the cortical node, however, is typically strongest during the UP state, which follows a DOWN state "window of opportunity" for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.

neuroscience↗

bioRxiv2021

A Biophysical Model of Nonquantal Transmission at the Vestibular Hair Cell-Calyx Synapse: KLV currents Modulate Fast Electrical and Slow K+ potentials in the Synaptic Cleft

Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal called a calyx. The vestibular hair cell-calyx synapse supports a mysterious form of electrical transmission that does not involve gap junctions termed nonquantal transmission (NQT). The NQT mechanism is thought to involve the flow of ions from the pre-synaptic hair cell to the post-synaptic calyx through low-voltage-activated channels driven by changes in cleft [K+] as K+ exits the hair cell. However, this hypothesis has not been tested with a quantitative model and the possible role of an electrical potential in the cleft has remained speculative. Here we present a computational model that captures salient experimental observations of NQT and identifies overlooked features that corroborate the existence of an electrical potential ({phi}) in the synaptic cleft. We show that changes in cleft{phi} reduce transmission latency and illustrate the relative contributions of both cleft [K+] and{phi} to the gain and phase of NQT. We further demonstrate that the magnitude and speed of NQT depend on calyx morphology and that increasing calyx height reduces action potential latency in the calyx afferent. These predictions are consistent with the idea that the calyx evolved to enhance NQT and speed up vestibular signals that drive neural circuits controlling gaze, balance, and orientation. Significance StatementThe ability of the vestibular system to drive the fastest reflexes in the nervous system depends on rapid transmission of mechanosensory signals at vestibular hair cell synapses. In mammals and other amniotes, afferent neurons form unusually large calyx terminals on certain hair cells, and communication at these synapses includes nonquantal transmission (NQT), which avoids the synaptic delay of quantal transmission. We present a quantitative model that shows how NQT depends on the extent of the calyx covering the hair cell and attributes the short latency of NQT to changes in synaptic cleft electrical potential caused by current flowing through open potassium channels in the hair cell. This previously undescribed mechanism may act at other synapses.

neuroscience↗

bioRxiv2021

Putting the theory into 'burstlet theory': A biophysical model of bursts and burstlets in the respiratory preBötzinger complex

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBotzinger complex (preBotC). In in vitro slice preparations containing the preBotC, extracellular potassium must be elevated above physiological levels (to 7 - 9 mM) to observe regular rhythmic respiratory motor output in the hypoglossal nerve to which the preBotC projects. Reexamination of how extracellular K+ affects preBotC neuronal activity has revealed that low amplitude oscillations persist at physiological levels. These oscillatory events are sub-threshold from the standpoint of transmission to motor output and are dubbed burstlets. Burstlets arise from synchronized neural activity in a rhythmogenic neuronal subpopulation within the preBotC that in some instances may fail to recruit the larger network events, or bursts, required to generate motor output. The fraction of subthreshold preBotC oscillatory events (burstlet fraction) decreases sigmoidally with increasing extracellular potassium. These observations underlie the burstlet theory of respiratory rhythm generation. Experimental and computational studies have suggested that recruitment of the non-rhythmogenic component of the preBotC population requires intracellular Ca2+ dynamics and activation of a calcium-activated non-selective cationic current. In this computational study, we show how intracellular calcium dynamics driven by synaptically triggered Ca2+ influx as well as Ca2+ release/uptake by the endoplasmic reticulum in conjunction with a calcium-activated non-selective cationic current can explain all of the key observations underlying the burstlet theory of respiratory rhythm generation. Thus, we provide a mechanistic basis to unify the experimental findings on rhythm generation and motor output recruitment in the preBotC.

neuroscience↗

bioRxiv2022

PPMO-mediated exon skipping induces uniform sarcolemmal dystrophin rescue with dose-dependent restoration of circulating microRNA biomarkers and muscle biophysical properties

Duchenne muscular dystrophy (DMD) is a paediatric muscle-wasting disorder caused by genetic loss of the gene encoding the dystrophin protein. Therapies that restore dystrophin expression are presumed to correct the disease, with antisense-mediated exon skipping being the leading approach. In this study, we aimed to determine whether exon skipping using a peptide-phosphorodiamidate morpholino oligonucleotide (PPMO) conjugate results in dose-dependent restoration of uniform dystrophin localization, together with correction of putative DMD serum and muscle biomarkers. To this end, dystrophin-deficient mdx mice were treated with a PPMO (Pip9b2-PMO) designed to induce Dmd exon 23 skipping and dystrophin rescue at single, ascending intravenous doses (3, 6, or 12 mg/kg) and sacrificed two weeks later. Dose-dependent exon skipping and dystrophin protein restoration were observed. Importantly, dystrophin expression was uniformly distributed at the sarcolemma of corrected myofibers at all doses. The abundance of serum microRNA biomarkers (i.e. miR-1a-3p, miR-133a-3p, miR-206-3p, miR-483-3p) and creatinine kinase were restored towards wild-type levels after treatment in a dose-dependent manner. All biomarkers were strongly anti-correlated with both exon skipping level and dystrophin expression. Dystrophin rescue was also strongly positively correlated with muscle stiffness (i.e. Youngs modulus) as determined by atomic force microscopy (AFM) nanoindentation assay. These data demonstrate that PPMO-mediated exon skipping generates myofibers with uniform dystrophin expression, and that both serum miRNA biomarkers and muscle AFM have potential utility as pharmacodynamic biomarkers of dystrophin restoration therapy in the context of DMD.

molecular biology↗

bioRxiv2022

Uncovering circuit mechanisms of current sinksand sources with biophysical simulations ofprimary visual cortex

Local field potential (LFP) recordings reflect the dynamics of the current source density (CSD) in brain tissue. The synaptic, cellular and circuit contributions to current sinks and sources are ill-understood. We investigated these in mouse primary visual cortex using public Neuropixels recordings and a detailed circuit model based on simulating the Hodgkin-Huxley dynamics of numerous cortical neurons belonging to 17 cell types. The model simultaneously captured spiking and CSD responses and demonstrated a two-way dissociation: Firing rates are altered with minor effects on the CSD pattern by adjusting synaptic weights, and CSD is altered with minor effects on firing rates by adjusting synaptic placement on the dendrites. We describe how thalamocortical inputs and recurrent connections sculpt specific sinks and sources early in the visual response, whereas cortical feedback crucially alters them in later stages. Our findings show that CSD analysis provides powerful constraints for modeling beyond those from considering spikes.

neuroscience↗