Biology subjects

Matsui, T.

Publications and source records attributed to Matsui, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Computational design of a versatile, zero-radius proximity labeling enzyme

The ability to map protein interactomes and organelle proteomes is foundational for achieving a molecular understanding of living cells. Proximity labeling (PL) provides a powerful strategy for this, but existing enzymes and photocatalysts are limited by their spatial resolution, reliance on biotin, and/or in vivo compatibility. Here we report FlexID, an engineered promiscuous ligase that catalyzes the rapid attachment of diverse small-molecule probes to proximal endogenous proteins. Critically, FlexID operates through a zero-radius, direct-contact mechanism, offering superior spatial precision compared to existing PL tools. We engineered FlexID by combining the strengths of sequence- and structure-trained computational models to enhance its catalytic activity and structural stability. Biophysical analysis revealed that specific conformational changes in FlexID improve its ability to recognize diverse target proteins while simultaneously preventing the premature release of the reactive intermediate. We demonstrate FlexID's versatility through in vivo proximity labeling, comprehensive organelle proteome mapping, and a high-throughput, fluorescence-based screen for molecular glues. Our work shows that computational methods can be harnessed to create mechanistically distinct PL enzymes and establishes FlexID as a flexible, high-resolution tool for mapping protein interactions and proteomes in living cells.

bioengineering↗

bioRxiv2026

A versatile fluorescent probe for imaging fibrillar collagen during avian morphogenesis

Fibrillar collagen architecture provides a fundamental structural framework for vertebrate tissues. Understanding how collagen matrices are organized and remodeled requires high-resolution imaging approaches capable of resolving their three-dimensional architecture and developmental dynamics in vivo. We previously established that the fluorescent probe DAF FM DA enables sensitive visualization of collagen structures in zebrafish, amphibian, and mouse tissues. However, whether this approach is applicable to avian embryos - an important model system in morphogenesis research - has remained unclear. Here we demonstrate that DAF FM DA specifically and robustly labels collagen matrices in quail embryonic tissues. Using this method, lattice like stromal networks in the cornea and spongy matrices in the limb cartilage primordium were clearly visualized throughout deep tissue regions. This imaging strategy provides a practical and versatile tool for investigating collagen matrix development in vertebrate morphogenesis using avian embryos.

developmental biology↗

bioRxiv2026

Antioxidant capacity of Catechinopyranocyanidins derived from adzuki beans

Catechinopyranocyanidins (Cpcs) which consist of diastereomers A and B are pigments derived from adzuki beans and are compounds in which the catechin and cyanidin skeletons are condensed to a pyrano ring. While catechins and anthocyanidins possess high antioxidant capacity, the physiological functions of Cpcs remains unclear. In this study, the antioxidant capacity of Cpcs was evaluated by in vitro antioxidant assays and by assessing their cytoprotective activity against oxidative stress in normal human dermal fibroblasts (NHDFs). Antioxidant capacity based on the hydrogen atom transfer (HAT) mechanism, as assessed by the ORAC assay revealed that Cpcs exhibit 14.1 mol TE/mol (Trolox equivalent antioxidant capacity: TEAC). Meanwhile, capacity based on the single electron transfer (SET) mechanism, as assessed by the DPPH, ABTS and CUPRAC assays revealed, they exhibit 2.1-3.6 mol TE/mol. Since TEAC value of Cpcs demonstrated by the HAT based mechanism higher than its SET based oxidative capacity suggesting that the antioxidant capacity of Cpcs is driven by the HAT mechanism. In cell culture experiments, Cpcs ameliorate cell toxicity in rotenone-induced injury model, suggesting to cytoprotective activity against mitochondrial dysfunction-dependent apoptosis. These results reveal novel physiological functions of Cpcs which may serve as a design guideline for elucidating in vivo dynamics based on antioxidant mechanisms.

biochemistry↗

bioRxiv2026

Fgf3 and Fgf10a regulate neuronal fasciculation through Schwann cell proliferation and infiltration in zebrafish posterior lateral line

BackgroundDuring development, axons are organized into bundles, a process known as axonal fasciculation. The zebrafish lateral line nerve has been used as a model to study axonal fasciculation; however, the underlying mechanisms are not yet fully understood. Although Fgf3 and Fgf10a are well known to regulate the migration of the lateral line primordium along which the lateral line nerve projects, their roles in the organization of the lateral line nerve itself have not been clarified. Resultsfgf3,10a double mutants exhibited lateral line axonal defasciculation accompanied by an increased number of Schwann cells. Live imaging revealed a marked increase in Schwann cell proliferation and demonstrated that newly divided Schwann cells migrate along axons and infiltrate interaxonal spaces, thereby expanding these spaces and disrupting axonal fasciculation. Pharmacological manipulations further implicated a contribution of Nrg1-ErbB signaling to this phenotype. ConclusionsOur findings suggest that Fgf3 and Fgf10a are required to restrict Schwann cell proliferation and infiltration, thereby ensuring axonal fasciculation during lateral line development.

developmental biology↗

bioRxiv2026

System identification and surrogate data analyses imply approximate Gaussianity and non-stationarity of resting-brain dynamics

Compared with model-based and phenomenological descriptions of the spatiotemporal dynamics of resting-brain activity, statistical characterizations of resting-state fMRI (rs-fMRI) data remain relatively underexplored. Some sophisticated analysis techniques, such as Mapper-based topological data analysis (TDA) and innovation-driven coactivation pattern analysis (iCAP), can distinguish real data from phase-randomized (PR) surrogates, suggesting that rs-fMRI data are not as simple as stationary Gaussian processes. However, the exact statistical properties that distinguish real rs-fMRI data from PR surrogates have not yet been determined. In this study, we conducted system identification analysis and surrogate data analysis to specify key statistical properties that allow TDA and iCAP to discriminate real rs-fMRI data from PR surrogates. We first analyzed rs-fMRI data concatenated across scans using autoregressive (AR) modeling and found that the scan-concatenated rs-fMRI data were weakly non-Gaussian. However, non-Gaussianity alone was insufficient to reproduce realistic TDA and iCAP results because of non-stationarity across scans. AR modeling of single-scan data revealed that rs-fMRI data were statistically indistinguishable from a Gaussian distribution within a single scan, although TDA and iCAP results still differed between the real data and PR surrogates. A new surrogate dataset designed to preserve non-stationarity successfully reproduced realistic TDA and iCAP results, suggesting that TDA and iCAP likely capture the non-stationarity of rs-fMRI data to distinguish it from PR surrogates. Together, these results indicate approximate Gaussianity and non-stationarity in rs-fMRI data, providing a data-driven and statistical characterization of resting-state brain activity that can serve as a quantitative reference for whole brain simulations and generative models.

neuroscience↗

bioRxiv2026

Acute Milk-Protein Intake Enhances Pupil-Linked Executive Function and Esports Performance During Prolonged Play

Prolonged esports play induces cognitive fatigue that is not fully captured by subjective awareness, motivating practical, non-stimulant nutritional strategies supported by objective physiological markers. We here tested whether acute milk protein intake attenuates fatigue-related physiological responses during prolonged esports play and supports subjective state, executive control, and in-game performance. In a randomized, single-blind (assessor-blind), energy-matched controlled crossover study, 15 healthy young adults with esports experience completed two sessions in which they consumed either a milk protein drink or an energy-matched apple juice control before a 3-h virtual soccer task. Physiological measures included pupillometry during gameplay, salivary cortisol, continuous interstitial glucose monitoring, and heart rate. Subjective ratings (VAS) and executive function (flanker task) were assessed across post-ingestion time points, and in-game performance metrics were aggregated within hourly gameplay blocks. Milk protein intake was associated with a coherent pattern of physiological advantages, including larger pupil diameter during gameplay, smoother interstitial glucose dynamics, and lower salivary cortisol, while heart rate showed time-dependent changes without a clear condition effect. These physiological changes co-occurred with higher enjoyment and lower hunger, improved flanker performance, and condition-dependent improvements in in-game performance, most notably higher shot success rate. Additionally, pupil diameter during gameplay was associated with inhibitory-control efficiency on the flanker task. These findings suggest that acute milk protein intake may serve as a practical, non-stimulant nutritional strategy to sustain physiological state and cognitive-behavioral performance during prolonged esports (virtual soccer) play. Highlights- Prolonged esports play models modern digital cognitive activity and cognitive fatigue. - Acute milk protein intake increases pupil diameter during prolonged esports play. - Interstitial glucose dynamics are smoother and salivary cortisol is lower with milk protein. - Enjoyment increases and hunger decreases during 3 h of virtual soccer play. - Executive function and in-game performance improve, most notably shot success rate.

neuroscience↗

bioRxiv2026

Sowing date effects on anther dehiscence, pollen germination on the stigma, and fertility under heat in Japanese rice

Heat-tolerant rice cultivars are essential for mitigating global warming impacts. Basal anther dehiscence length (BDL) is a promising visible morphological marker for heat tolerance through stable pollination. We investigated the effects of sowing date on anther morphology, pollination, and fertility under controlled high-temperature conditions (35, 37, or 39 {degrees}C at flowering). Three japonica cultivars-- Akitakomachi (early heading), Koshihikari (medium), and Hatsushimo (late)--were sown monthly over 3 months and grown in pots. At heading, the plants were exposed to the temperature treatments for 3 days, and the proportion of florets with [≥]10 germinated pollen grains on the stigma (GP10) and seed set were assessed. Among anther traits, BDL showed the greatest variation, with all cultivars from the second sowing exhibiting the shortest BDL. Analysis of variance revealed significant effects of genotype, sowing date, and their interaction on anther traits and fertility. Regression analysis indicated that fertility was associated with GP10, with BDL contributing significantly to GP10 in the late-heading Hatsushimo, together with maximum temperature at flowering. Thus, both genotype and environment shape anther morphology, pollination, and fertility, indicating that BDL plasticity and genotype-specific environmental responses must be carefully considered when using BDL as a breeding marker for heat tolerance. HighlightVariation in sowing date significantly affects anther morphology and heat tolerance in rice. Genotype-specific responses to the growing environment require careful consideration for reliable breeding assessments.

plant biology↗

bioRxiv2026

DIA-MS based plasma peptidomic workflow for profiling organ-derived peptides

Plasma contains diverse bioactive peptides that play crucial roles in maintaining homeostasis and regulating disease responses. However, the presence of peptides derived from high-abundance proteins such as albumin makes comprehensive analysis of native peptides secreted by organs challenging. This study aimed to establish a highly sensitive plasma peptidomic approach by combining data-independent acquisition (DIA) with spectral libraries of plasma and organs. First, peptides were extracted from plasma and eleven organ types using a high-yield peptide extraction method, the differential solubilization method. These peptides were then measured via data-dependent acquisition (DDA) analysis using a timsTOF HT for constructing empirical spectral library. Subsequently, DIA-MS data from plasma samples were measured and analyzed using this spectral library. This strategy achieved identification of, on average, over 5,500 peptides per run, with over 2,000 organ-derived peptides including 19 known bioactive peptides. The novel strategy proposed here enables highly sensitive quantitative analysis of organ-derived peptides in plasma, linking them to their secreting organs. It is expected to substantially contribute not only to the discovery of biomarkers and novel bioactive peptides but also to elucidating the pathophysiology of systemic diseases.

biochemistry↗

bioRxiv2026

Joint Pupillometry and Heart Rate Monitoring Identify Zone-Like High Performance in Esports

Modern digital activities, such as esports, combine intense cognitive demands with limited whole-body movement, weakening calibration between subjective awareness and functional states. Cognitive deterioration during prolonged esports precedes subjective fatigue, suggesting subjective flow likewise fails to reveal efficient cognitive-sensorimotor performance states. Although efficient cognitive-sensorimotor performance may involve central-autonomic coordination reflected in intrapersonal pupil-heart synchrony, the functional role of this coordination remains largely unknown. We hypothesized that, during esports play, central-autonomic coordination contributes to an efficient cognitive-sensorimotor performance state that subjective flow fails to capture. Fourteen young men completed sessions involving watching a fighting game, playing against a computer-controlled opponent, and competing against another person. We assessed pupil diameter, heart rate, subjective flow, subjective workload, and objective in-game performance. Esports competition increased subjective flow without improving objective in-game performance and reduced combat efficiency, demonstrating a subjectively optimal experience need not signal high in-game performance efficiency. Data-driven clustering identified a low-reactivity state combining superior objective in-game performance with lower subjective workload. This state showed selectively sustained pupil-heart synchrony. Reduced workload partly accounted for the association between pupil-heart synchrony and objective in-game performance. Our findings suggest that individuals fail to recognize periods of high in-game performance efficiency, as cognitive deterioration escapes awareness during prolonged esports. This efficiency is associated with pupil-heart synchrony, supporting the hypothesis that central-autonomic coordination contributes to an efficient cognitive-sensorimotor performance state. Pupil-heart synchrony may therefore serve as a mechanism-based biomarker for detecting efficient states beyond awareness, optimizing objective task performance and the timing of recovery in demanding digital environments.

neuroscience↗

bioRxiv2026

A Glycaemia-Prolonging Carbohydrate Gel Reduces Hunger and Cognitive Fatigue During Prolonged Esports Play

AbstractProlonged esports play can induce cognitive fatigue by placing sustained demands on executive control, decision-making, and stress regulation. Since the brain relies primarily on glucose as an immediate energy source, we hypothesized that a carbohydrate gel designed to prolong post-ingestion glycaemia stabilizes interstitial glucose, attenuates hunger and cognitive fatigue, and helps preserve performance during extended esports play. Eleven healthy young men completed a randomized, double-blind crossover study with two sessions in which they ingested one of two carbohydrate gels matched for total energy and total carbohydrate but differing in carbohydrate composition (high-fructose corn syrup [HFCS]-dominant vs maltodextrin [MDX]-dominant) before gameplay. Interstitial glucose was monitored continuously, while hunger, salivary cortisol, pupil diameter, executive function, and in-game performance were assessed repeatedly. Compared with the control (HFCS-dominant) condition, the glycaemia-prolonging formulation maintained higher interstitial glucose levels during the later phase of gameplay, blunted the progressive increase in hunger, and attenuated cortisol responses. These physiological and subjective advantages were accompanied by better executive control and more adaptive defensive behaviors in-game, including fewer fouls and more interceptions. In contrast, pupil diameter, an index of global arousal, remained unchanged across conditions, suggesting that benefits were not driven by altered arousal but by improved glycaemic stability and appetite regulation. These findings indicate that a carbohydrate formulation that prolongs glycaemia can reduce hunger-linked cognitive fatigue and support task-relevant behavior during prolonged esports play. This low-burden nutritional strategy may help sustain mental performance during prolonged digital activities that impose high cognitive demands. Highlights- A glycaemia-prolonging gel maintained higher interstitial glucose late in esports play - Hunger and salivary cortisol increased less with the glycaemia-prolonging formulation - Executive control and defensive performance improved (fewer fouls, more interceptions) - Pupil diameter was unchanged, suggesting benefits were not driven by altered arousal - A low-burden, glycaemia-stabilizing strategy may help sustain cognitive stamina

neuroscience↗

bioRxiv2026

Sparkling Water Co-Consumption Enhances Oxytocin-Linked HR Synchrony and Social Connection in Live Sports Spectatorship

Live sport spectatorship can promote social connection, yet scalable, low-burden strategies to strengthen bonding in real-world spectator settings remain limited. We here tested the hypothesis that co-consuming sparkling water during spectating attenuates hunger and fatigue and strengthens enjoyment and perceived unity, potentially via HR synchrony linked to oxytocin dynamics. In an individually randomized field experiment at a collegiate womens basketball home game (sparkling water: n = 21; plain water: n = 19), spectators consumed 200 mL of sparkling water or plain water in synchrony before tip-off and before the end of halftime, with additional ad libitum intake of the assigned beverage permitted thereafter. We assessed acute freshness and hunger, repeated fatigue and enjoyment, interpersonal HR synchrony from the first half to 15-min post-game, perceived unity toward players and fellow spectators, and salivary oxytocin levels. Relative to plain water, sparkling water increased freshness and reduced hunger after intake, attenuated post-game fatigue, and enhanced enjoyment and perceived unity. HR synchrony was preserved in association with attenuated post-game fatigue after the game, and sustained synchrony was associated with higher perceived unity. Oxytocin decreased more in the sparkling-water group, and this decrease was associated with preserved HR synchrony as well as with changes in unity toward fellow fans. These findings support our hypothesis and suggest that co-consuming sparkling water serves as an alcohol-free, low-burden ritual to enhance social connection during and after live sport events. Highlights- Sparkling water increased freshness and reduced hunger after intake in spectators. - Sparkling water attenuated the post-game increase in subjective fatigue. - Sparkling water increased enjoyment and perceived unity. - Post-game HR synchrony was preserved in association with lower fatigue and higher unity. - Oxytocin decreased more with sparkling water and tracked HR synchrony and fan unity. - Co-consuming sparkling water is a low-burden, alcohol-free ritual for social connection.

neuroscience↗

bioRxiv2025

2-Mercaptoethanol/DMSO workflow enables highly reproducible quantitative proteomics

Proteomics provides a systematic and high-throughput approach to comprehensively characterize protein networks, enabling insights into cellular functions and disease mechanisms. Carbamidomethylation using iodoacetamide (IAA), a common method for cysteine alkylation, is known to cause nonspecific modifications that increase MS spectral complexity and reduce quantitative accuracy. Here, we extended our 2-mercaptoethanol (2-ME) adduction method, enhanced by dimethyl sulfoxide (DMSO), from single-protein applications to a proteome-wide workflow. Mouse liver proteomes were processed using either 2-ME/DMSO or conventional IAA treatment, followed by LC-MS/MS analysis. The optimized 2-ME treatment increased the number of cysteine-modified peptides by 1.6-1.9-fold. Although total protein identifications were comparable, 77% of proteins exhibited improved sequence coverage. Quantitative reproducibility was also enhanced, with peptides quantified coefficient of variation (CV) [≤] 20% increasing from 61.5% (IAA) to 86.1% (2-ME), and proteins from 80.6% to 93.5%. Application of the workflow to an ovarian clear cell carcinoma reliably detected cisplatin-induced alterations. The 2-ME/DMSO workflow offers a simple and highly reproducible proteomics strategy for accurate quantitative proteomics.

biochemistry↗

bioRxiv2025

Structure-Function Coupling Aligns with a Unimodal-to-Transmodal Gradient in the Mouse Cortex

Understanding how anatomical connectivity shapes brain activity is essential for clarifying brain function and disorders. In the human brain, the regional heterogeneity in structure-function (S-F) coupling is well characterized by measuring correlations between structural and functional connectivity. However, it remains unclear whether the same principles apply to the mouse cortex, where biological mechanisms can be studied directly. Here, we mapped S-F coupling across the mouse cortex by combining high-resolution structural connectivity derived from axonal tracing with resting-state functional connectivity measured by wide-field calcium imaging. Our findings revealed that structural connectivity imposes a robust yet regionally variable constraint on functional connectivity. As in humans, the S-F coupling was strong in primary sensorimotor areas and weaker in association areas, demonstrating a gradient from unimodal-to-transmodal cortical organization. This spatial variation covaried with intrinsic cellular properties, including myelination, excitation-inhibition balance, synaptic density, and gene expression profiles, but did not align with the anatomically defined cortical hierarchy. Our findings highlight graded S-F coupling as a common organizational principle in both the mouse and human cortex, providing a framework for future mechanistic studies using mouse models.

neuroscience↗

bioRxiv2025

Epigenomic and transcriptomic germ-free ageing atlas reveals sterile inflammation as an intrinsic ageing feature

Inflammageing is a hallmark of ageing. Commensal microbiota plays crucial roles in maintaining tissue homeostasis, yet its impact on cellular ageing and inflammageing remains poorly understood. Here we present a comprehensive single-cell epigenomic and transcriptomic atlas of tissues from mice aged under specific pathogen-free (SPF) or germ-free (GF) conditions. Microbiota conferred beneficial effects in young mice but accelerated various ageing features in old, such as age-related AP-1 pathway upregulation, senescence and transcriptomic alterations, likely due to age-associated dysbiosis. Strikingly, inflammatory signatures persisted across cell types in aged GF mouse tissues, establishing sterile inflammation as an intrinsic feature of ageing. Age-associated B cells expanded equally under GF and SPF conditions, raising the possibility that they function as intrinsic, microbiota-independent drivers of inflammageing and potential therapeutic targets. The atlas provides a resource for distinguishing intrinsic ageing features from those modulated by the microbiota, illuminating mechanisms of cellular ageing and potential anti-ageing interventions. HighlightsSterile inflammation and age-associated B cell expansion are prominent intrinsic ageing features The upregulation of age-associated AP-1 pathways and senescence of alveolar macrophages are attenuated in germ-free condition Germ-free condition induces premature ageing-like features in young mouse tissues but delays ageing features in old mice across multiple cell types

genomics↗

bioRxiv2025

Sparkling Water Limits Cognitive Fatigue with Stable Pupil Diameter during Real World Esports Training

Prolonged esports play induces cognitive fatigue with reduced executive function and pupil constriction as a neurobiomarker of prefrontal activity across expertise levels. Since this pupil-linked cognitive fatigue is mitigated by sparkling water intake in casual players, we hypothesized that sparkling water prevents cognitive fatigue and sustains esports performance in esports athletes under real training conditions that reflect competitive practice. To test this hypothesis, nineteen hardcore esports players participated in a randomized crossover trial. Each completed two 3-hour sessions of head-to-head virtual football matches while consuming either sparkling water or plain water. Subjective fatigue, enjoyment, and executive function (flanker task) were assessed, and pupil diameter, heart rate, and salivary cortisol were continuously monitored. In-game performance was also recorded. Accuracy declined and pupil constriction progressed under the plain water condition, whereas executive accuracy was preserved and pupil diameter was maintained over the three-hour session in the sparkling water condition. Subjective ratings of fatigue and enjoyment increased similarly in both conditions. Heart rate, including both mean and peak values, and salivary cortisol concentrations showed no significant differences between conditions. In terms of in-game performance, goals, passes, and interceptions did not differ between conditions, whereas the number of fouls was lower and the number of shots was higher in the sparkling water condition. These findings demonstrate that sparkling water mitigates cognitive fatigue and sustains esports performance in esports athletes under real training conditions. As a caffeine- and sugar-free beverage, sparkling water may serve as a practical, low-risk intervention for managing cognitive fatigue and supporting daily practice in modern esports settings.

neuroscience↗

bioRxiv2025

Live sports spectating promotes oxytocin dynamics and heart rate synchrony in casual fans

Oxytocin has been proposed as a pharmacological target for social dysfunction. However, clinical trials of exogenous oxytocin have yielded modest and inconsistent benefits, highlighting the need for naturalistic, non-pharmacological approaches that recruit endogenous oxytocin. This prospective observational field study examined whether live sports spectating in a modest collegiate setting engages endogenous oxytocin and heart rate synchrony, and how these processes relate to social bonding. Sixty casual spectators at two university basketball games provided salivary samples for oxytocin and cortisol and completed psychological questionnaires before the game, at halftime, and after the game, while heart rate was continuously recorded. Oxytocin dynamics were baseline dependent: individuals with low pre-game oxytocin showed clear increases during spectating, whereas those with high pre-game oxytocin maintained elevated concentrations; across both groups, cortisol decreased and the oxytocin-to-cortisol ratio increased, indicating a shift toward an oxytocin-dominant, low-stress hormonal profile. Live spectating also enhanced heart rate synchrony between spectators, and higher oxytocin levels and stronger synchrony were associated with greater enjoyment, stronger unity with players and fellow fans, higher flow, and stronger intention to revisit. Mediation analyses indicated that perceived unity mediated links between physiological responses and experiential outcomes. These findings identify coordinated oxytocin dynamics and physiological synchrony as candidate mechanisms through which live sports spectating can foster social connection and positive psychological states in everyday, low-stakes settings. Live sports events may represent a simple, scalable non-pharmacological approach to engaging oxytocin-related systems and interpersonal synchrony to promote social connection in everyday life.

neuroscience↗

bioRxiv2025

Lenacapavir binding to immature Gag triggers the emergence of giant HIV-1 virions

Lenacapavir (LEN), a potent capsid inhibitor, suppresses reverse transcription and nuclear import by disrupting capsid core formation in human immunodeficiency virus type 1 (HIV-1). However, its effect on the late-stage viral assembly remains unclear. Although p24 ELISA suggested that LEN inhibited HIV-1, both RT-dPCR and Vpr-HiBiT assays indicated no reduction in the viral output. This discrepancy was attributed to LEN-induced epitope masking of p24, which was reversed by altered sample processing. Furthermore, LEN induced numerous abnormal, discrete clusters of Gag at the plasma membrane. Mass photometry and transmission electron microscopy revealed heterogeneous viral-like particles (LENiVLPs; diameter >200 nm), containing both Gag and Env proteins. Although LENiVLPs retained membrane fusion capability, they were non-infectious owing to post-entry defects. Thus, LEN binds to the precursor Gag and promotes aberrant particle formation, offering novel insights that could guide the development of next-generation LEN-based therapeutics targeting the late stages of the viral life cycle.

microbiology↗

bioRxiv2025

Dissecting Molecular Origins of the Mechano-Adaptive Behaviors of Actomyosin Bundles

Actomyosin bundles, composed mainly of actin filaments, myosin II filaments, and actin cross-linking proteins, are central to force generation and maintenance in non-striated muscle cells. Actomyosin bundles exhibit diverse mechano-adaptive responses to external mechanical cues. However, the molecular mechanisms underlying such adaptability remain poorly understood. In this study, we employed experiments and agent-based simulations to illuminate how actomyosin bundles adapt to complex mechanical perturbations. Our experiments revealed that individual stress fibers isolated from cells, and thus operating independently of cellular regulation, exhibited buckling in response to rapid compressions following stretch, accompanied by gradual recovery to a straight configuration. Such buckling was not observed under slow compression, indicating that the bundles exhibit rate-dependent adaptive responses. These findings demonstrate that mechano-adaptive behavior is an intrinsic property of actomyosin bundles. Simulations successfully reproduced these rate-dependent behaviors intrinsic to actomyosin bundles and identified key factors determining the dependence. Bundle stiffness influenced the buckling-induced curvature but had little effect on the time required for recovery to straight configuration. Motor density did not alter the recovery time but significantly influenced the magnitude of tensile forces developed after full recovery. The recovery time was primarily governed by the motor walking rate and the applied compressive strain rate. This work reveals how intrinsic mechanics and motor activity drive actomyosin bundle behavior in cellular mechano-adaptation.

biophysics↗