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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Heart Rate n-Variability (HRnV): A Novel Representation of Beat-to-Beat Variation in Electrocardiography

Heart rate variability (HRV) is a widely adopted tool for evaluating changes in cardiac autonomic regulation. The majority of efforts have focused on developing methods to assess HRV by deriving sophisticated parameters with linear and nonlinear techniques and adopting advanced signal processing tools for efficient noise removal and accurate QRS detection. In this paper, we propose a novel representation of beat-to-beat variation in an electrocardiogram (ECG), called heart rate n-variability (HRnV), as an alternative to conventional HRV measures. We derived two novel HRnV measures based on non-overlapped and overlapped RR intervals. We also conducted a simulation study by using an ECG record from the MIT-BIH Normal Sinus Rhythm Database to demonstrate the feasibility of calculating HRnV parameters. Among the time domain parameters, we observed that the values were generally incremental with the increase in n. We observed the same trend of changes for the frequency domain parameters. In the nonlinear analysis, the differences between HRV and HRnV from Poincare plot measures were obvious, while those from entropy and detrended fluctuation analysis metrics were not. HRnV measures enable us to augment conventional HRV measures with additional parameters. Although issues remain to be addressed regarding HRnV, we hope to stimulate a new stream of research on this new representation of HRV. HRnV is an important addition to HRV and will contribute to extending the landscape of current studies on HRV.

bioengineering↗

bioRxiv2018

Liver ultrasound elastography for the evaluation of periportal fibrosis in schistosomiasis mansoni: A cross-sectional study

BackgroundARFI elastrography has been used as a noninvasive method to assess the severity of liver fibrosis in viral hepatitis, although with few studies in schistosomiasis mansoni. We aimed to evaluate the performance of point shear wave elastography (pSWE) for predicting significant periportal fibrosis (PPF) in schistosomotic patients and to determine its best cutoff point.\n\nMethodology/Principal findingsThis cross-sectional study included 358 adult schistosomotic patients subjected to US and pSWE on the right lobe. Two hundred two patients (62.0%) were women, with a median age of 54 (ranging 18-92) years. The pSWE measurements were compared to the US patterns of PPF, as gold standard, according to the Niamey classification. The performance of pSWE was calculated as the area under the ROC curve (AUC). Patients were further classified into two groups: 86 patients with mild PPF and 272 patients with significant PPF. The median pSWE of the significant fibrosis group was higher (1.40 m/s) than that of mild fibrosis group (1.14 m/s, p<0.001). AUC was 0.719 with [≤]1.11 m/s as the best cutoff value for excluding significant PPF. Sensitivity and negative predictive values were 80.5% and 40.5%, respectively. Whereas, for confirming significant PPF, the best cutoff value was >1.39 m/s, with specificity of 86.1% and positive predictive value of 92.0%.\n\nConclusions/SignificancepSWE was able to differentiate significant from mild PPF, with better performance to predict significant PPF.\n\nAuthor summaryIn the developing world, over 207 million people are infected with parasitic Schistosoma worms. Among the species of Schistosoma that infect humans Schistosoma mansoni is one of the most common causes of illness. Here, we investigated the performance of point shear wave elastography (pSWE) for predicting significant periportal fibrosis (PPF) in schistosomotic patients and to determine its best cutoff point. We examined 358 people from northeast of Brazil for Schistosoma infections. The present study showed that pSWE was able to differentiate significant from mild PPF, with better performance to predict significant PPF.

bioengineering↗

bioRxiv2018

On-ratio PDMS bonding for multilayer microfluidic device fabrication

Integrated elastomeric valves, also referred to as Quake valves, enable precise control and manipulation of fluid within microfluidic devices. Fabrication of such valves requires bonding of multiple layers of the silicone polymer polydimethylsiloxane (PDMS). The conventional method for PDMS-PDMS bonding is to use varied base to crosslinking agent ratios between layers, typically 20:1 and 5:1. This bonding technique, known as \"off-ratio bonding,\" provides strong, effective PDMS-PDMS bonding for multi-layer soft-lithography, but it can yield adverse PDMS material properties and can be wasteful of PDMS. Here we demonstrate the effectiveness of on-ratio PDMS bonding for multilayer soft lithography. We show the efficacy of this technique among common variants of PDMS: Sylgard 184, RTV 615, and Sylgard 182.

bioengineering↗

bioRxiv2018

Directed evolution of split APEX peroxidase

APEX is an engineered peroxidase that catalyzes the oxidation of a wide range of substrates, facilitating its use in a variety of applications, from subcellular staining for electron microscopy to proximity biotinylation for spatial proteomics and transcriptomics. To further advance the capabilities of APEX, we used directed evolution to engineer a split APEX tool (sAPEX). Twenty rounds of FACS-based selections from yeast-displayed fragment libraries, using three different yeast display configurations, produced a 200-amino acid N-terminal fragment (with 9 mutations relative to APEX2) called \"AP\" and a 50-amino acid C-terminal fragment called \"EX\". AP and EX fragments were each inactive on their own but reconstituted to give peroxidase activity when driven together by a molecular interaction. We demonstrate sAPEX reconstitution in the mammalian cytosol, on engineered RNA motifs within telomerase noncoding RNA, and at mitochondria-endoplasmic reticulum contact sites.

bioengineering↗

bioRxiv2018

Split Selectable Markers

Selectable markers are widely adopted in transgenesis and genome editing for selecting engineered cells with desired genotype but are limited in choices. We present here split selectable markers each allowing for selection of multiple "unlinked" transgenes in the context of lentivirus-mediated transgenesis as well as CRISPR/Cas-mediated biallelic knock-ins. Future development of split selectable markers may support enrichment or selection of "hyper-engineered" cells containing tens of transgenes or genetic modifications.

bioengineering↗

bioRxiv2018

NanoMEA: a versatile platform for high-throughput analysis of structure-function relationships in human stem cell-derived excitable cells and tissues

Somatic cells derived from human pluripotent stem cell (hPSC) sources hold significant potential as a means to improve current in vitro screening assays. However, their inconsistent ability to recapitulate the structural and functional characteristics of native cells has raised questions regarding their ability to accurately predict the functional behavior of human tissues when exposed to chemical or pathological insults. In addition, the lack of cytoskeletal organization within conventional culture platforms prevents analysis of how structural changes in human tissues affect functional performance. Using cation-permeable hydrogels, we describe the production of multiwell nanotopographically-patterned microelectrode arrays (nanoMEAs) for studying the effect of structural organization on hPSC-derived cardiomyocyte and neuronal function in vitro. We demonstrate that nanoscale topographic substrate cues promote the development of more ordered cardiac and neuronal monolayers while simultaneously enhancing cytoskeletal organization, protein expression patterns, and electrophysiological function in these cells. We then show that these phenotypic improvements act to alter the sensitivity of hPSC-derived cardiomyocytes to treatment with arrhythmogenic and conduction-blocking compounds that target structural features of the cardiomyocyte. Similarly, we demonstrate that neuron sensitivity to synaptic blockers is increased when cells are maintained on nanotopographically-patterned Nafion surfaces. The improved structural and functional capacity of hPSC-derived cardiomyocyte and neuronal populations maintained on nanoMEAs may have important implications for improving the predictive capabilities of cell-based electrophysiological assays used in preclinical screening applications.

bioengineering↗

bioRxiv2018

Exonuclease III (XthA) enforces in vivo DNA cloning of Escherichia coli to create cohesive ends

Escherichia coli has an ability to assemble DNA fragments with homologous overlapping sequences of 15-40 bp at each end. Several modified protocols have already been reported to improve this simple and useful DNA-cloning technology. However, the molecular mechanism by which E. coli accomplishes such cloning is still unknown. In this study, we provide evidence that the in vivo cloning of E. coli is independent of both RecA and RecET recombinase, but is dependent on XthA, a 3 to 5 exonuclease. Here, in vivo cloning of E. coli by XthA is referred to as iVEC (in vivo E. coli cloning). Next, we show that the iVEC activity is reduced by deletion of the C-terminal domain of DNA polymerase I (PolA). Collectively, these results suggest the following mechanism of iVEC. First, XthA resects the 3' ends of linear DNA fragments that are introduced into E. coli cells, resulting in exposure of the single-stranded 5' overhangs. Then, the complementary single-stranded DNA ends hybridize each other, and gaps are filled by DNA polymerase I. Elucidation of the iVEC mechanism at the molecular level would further advance the development of in vivo DNA-cloning technology. Already we have successfully demonstrated multiple-fragment assembly of up to seven fragments in combination with an effortless transformation procedure using a modified host strain for iVEC.\n\nImportanceCloning of a DNA fragment into a vector is one of the fundamental techniques in recombinant DNA technology. Recently, in vitro recombination of DNA fragments effectively joins multiple DNA fragments in place of the canonical method. Interestingly, E. coli can take up linear double-stranded vectors, insert DNA fragments and assemble them in vivo. The in vivo cloning have realized a high level of usability comparable to that by in vitro recombination reaction, since now it is only necessary to introduce PCR products into E. coli for the in vivo cloning. However, the mechanism of in vivo cloning is highly controversial. Here we clarified the fundamental mechanism underlying in vivo cloning of E. coli and also constructed an E. coli strain that was optimized for in vivo cloning.

bioengineering↗

bioRxiv2018

Stochastic models of the growth dynamics of some dendritic cells

Different models of tumor growth are considered. Some mathematical methods are developed to analyze the dynamics of mutations enabling cells in cancer patients to metas-tize. The mathematical models consist of some stochastic dynamical systems describing tumor cells and immune effectors. It is also considered a method to find the ideal outcome of some treatments. Some different types of dendritic cells are considered. The obtained results will help to find some suitable treatments,which can be successful in returning an aggressive tumor to its passive,non-immune evading state. The principle goal of this paper is to find ways to treat the cancer tumors before they can reach an advanced stage devel-opmen.\n\nAMS Subject Classifications92B05, 37C45.

bioengineering↗

bioRxiv2018

Validation of a low-cost, carbon dioxide-based cryoablation system for percutaneous tumor ablation

Breast cancer rates are rising in low- and middle-income countries (LMICs), yet there is a lack of accessible and cost-effective treatment. As a result, the cancer burden and death rates are highest in LMICs. In an effort to meet this need, our work presents the design and feasibility of a low-cost cryoablation system using widely-available carbon dioxide as the only consumable. This system uses an 8-gauge outer-diameter needle and Joule-Thomson expansion to percutaneously necrose tissue with cryoablation. Bench top experiments characterized temperature dynamics in ultrasound gel demonstrated that isotherms greater than 2 cm were formed. Further, this system was applied to mammary tumors in an in vivo rat model and necrosis was verified by histopathology. Finally, freezing capacity under a large heat load was assessed with an in vivo porcine study, where volumes of necrosis greater than 1.5 cm in diameter confirmed by histopathology were induced in a highly perfused liver after two 7-minute freeze cycles. These results demonstrate the feasibility of a carbon-dioxide based cryoablation system for improving solid tumor treatment options in resource-constrained environments.

bioengineering↗

bioRxiv2026

Comparative study of chlorophyll measurement in Physcomitrium patens moss using a conventional microscope adapted for combined 2D+1D imaging and spectral analysis

Imaging spectroscopy often requires expensive and complex equipment. Here we show a simple procedure for attaching a standard miniature fiber spectrometer to a conventional microscope, allowing easy integration of 2D imaging with 1D high-resolution spectral measurements. This combination provides much of the benefit of a full imaging spectrometer without the large equipment investment, and we provide instructions for modifying microscopes to this setup and the present measurements of living cells that demonstrate their performance. Using this setup, we compare the quantitative measurement of chlorophyll concentration in Physcomitrium patens moss using color imaging and spectral sampling.

bioengineering↗

bioRxiv2026

Whole-body Super-resolution Functional and Molecular Imaging with Panoramic Photoacoustic-Ultrasound Tomography

Photoacoustic (PA) and ultrasound (US) imaging provide complementary molecular, functional, and anatomical contrasts. Here, we present a panoramic PA-US imaging platform that integrates multispectral PA computed tomography (PACT) along with reflection-mode and transmission-mode US imaging through a single shared full-ring ultrasound array. We employ an ultrafast planewave transmission scheme in reflection-mode US for power Doppler (PWD) imaging and ultrasound localization microscopy (ULM). Additionally, we use the transmission-mode US to reconstruct a spatially resolved speed of sound (SoS) map that corrects both PA and US reconstruction. Such correction sharpens the resolution of PACT, suppresses the artifacts of PWD, and improves microbubble localization of ULM. Elevational scanning further enables whole-body volumetric imaging with co-registered PA and US contrasts. The integrated system maps photoswitchable DrBphP1-expressing tumors alongside their blood perfusion and oxygenation environment. Applying the platform to monitor unilateral renal ischemia-reperfusion injury, we report that microvascular perfusion and renal oxygenation recover at different rates. Collectively, we demonstrate that the integrated PA-US imaging platform provides a unified framework for multiparametric study of anatomy, perfusion, microvascular flow, oxygenation, and molecular activities.

bioengineering↗

bioRxiv2026

Influence of trunk posture on spinal loading and paraspinal muscle forces in adolescent idiopathic scoliosis: a subject-specific musculoskeletal modelling study

Adolescent idiopathic scoliosis (AIS) alters spinal geometry and may influence the biomechanical response of the spine during functional postures. However, posture-dependent changes in spinal loading and paraspinal muscle forces in AIS remain poorly understood. This study investigated the effects of trunk posture on intervertebral loading and paraspinal muscle forces using a subject-specific musculoskeletal model of an adolescent with AIS. The spinal deformity was reconstructed from biplanar radiographs and incorporated into a full-body musculoskeletal model. Flexion, extension, lateral bending, and axial rotation were simulated at three incremental magnitudes, with motion distributed across the thoracolumbar spine. Intervertebral compressive and lateral forces around the curve apex and forces in the erector spinae (ES) and multifidus (MF) muscles were evaluated. Trunk flexion produced the greatest compressive loading, reaching 337 N at the curve apex and 372 N two levels below the apex at 30{degrees} flexion. Lateral bending produced pronounced direction-dependent loading: concave-side bending increased lateral forces, whereas convex-side bending increased compressive forces. Axial rotation produced similar but smaller direction-dependent changes. Paraspinal muscle forces were consistently asymmetric, with concave-side dominance of the ES and convex-side dominance of the MF. Flexion and convex-sided movements generally produced greater muscle imbalance, while increasing posture magnitude amplified spinal loading and muscle forces. These findings demonstrate that trunk posture, movement direction, and magnitude substantially influence the biomechanical environment of the scoliotic spine and should be considered when evaluating spinal mechanics in AIS.

bioengineering↗

bioRxiv2026

Near-infrared optoacoustic modulation of the blood-brain barrier permeability using size-tuned hyperbranched gold nanoconstructs

The blood-brain barrier (BBB) constitutes a major bottleneck for the systemic delivery of most therapeutic agents to the central nervous system. Here, we report near-infrared reversible optoacoustic modulation of the BBB permeability (NIR-ROAMBBB), leveraging endothelial tight junction targeting hyperbranched gold nanoconstructs (HBGNCs) to amplify localized optoacoustic transduction under femtosecond laser excitation. We first synthesized HBGNCs with tunable particle sizes (62-150 nm) and consistent branch morphologies via a seed-mediated growth approach, and uncovered a non-monotonic relationship between particle dimension and optoacoustic output, where the 62 nm HBGNCs generated nearly twofold stronger optoacoustic signal than gold nanorods and gold nanostars under matched excitations. Conjugation with BV11 antibodies against junctional adhesion molecule A increased HBGNC endothelial association and cerebral accumulation, enabling focal and fluence-dependent transient BBB opening (3-6 h) under 800 nm femtosecond pulsed laser excitation, as validated by in vitro trans-endothelial electrical resistance measurements, ex vivo Evans blue extravasation staining, and in vivo NIR imaging. Featuring deep tissue penetration of NIR light, robust optoacoustic conversion of HBGNCs, and negligible femtosecond laser-induced photothermal damage, this non-invasive strategy enables precise focal modulation of BBB permeability and potential drug delivery.

bioengineering↗

bioRxiv2026

3D ultrasound fascicle tractography for objective muscle architecture analysis.

Muscle architecture shapes muscle function and changes with age, growth, training and disease, yet quantifying three-dimensional (3D) muscle architecture in vivo remains challenging. We introduce a hybrid fascicle tractography approach for freehand 3D ultrasound data that accurately reconstructs 3D muscle fascicles with respect to an objective, anatomically relevant coordinate system defined by the muscle's central aponeurosis. The hybrid approach combines Hessian-based fascicle detection with wavelet-based refinement to generate volumetric fascicle orientations. In a synthetic dataset with known ground truth, fascicle orientations and lengths were estimated with errors of [≤]2{degrees} and ~1.5%, respectively. In vivo, the approach detected physiologically plausible fascicle lengthening in the human tibialis anterior following a passive plantar flexion rotation, whereas diffusion tensor imaging of the same muscle did not. The proposed method enables anatomically relevant, objective and non-invasive quantification of 3D muscle architecture in vivo, providing a practical framework for applications in clinical and applied muscle physiology.

bioengineering↗

bioRxiv2026

Programmable Antibody-DNA Conjugation via HUH-Tags Enables Quantitative Measurement of Receptor-Specific Adhesion Dynamics

Antibody-DNA oligonucleotide conjugates (AOCs) are widely used for molecular assembly and cellular analysis, yet current approaches for generating these conjugates often rely on nonspecific chemistries that produce heterogeneous products. Here, we present two complementary strategies for generating site-specific AOCs using covalent DNA-linking HUH endonucleases. In one approach, recombinant antibodies are genetically fused to HUH-tags to enable direct, site-specific DNA conjugation. In the second, off-the-shelf antibodies are indirectly linked to HUH-tags using a photocrosslinkable Protein G-HUH fusion, enabling covalent Fc-directed attachment. Both strategies yield homogeneous AOCs while preserving antigen binding affinity. We apply these conjugates to a DNA-based mechanochemical assay, termed rupture-and-deliver tension gauge tethers (RAD-TGTs), which converts receptor-mediated adhesion forces into intracellular delivery of a fluorescent oligonucleotide payload. By tuning duplex stability, we define adhesion dynamics across multiple mechanical regimes. Using HER2- and beta1-integrin-targeting AOCs, we identify receptor-specific adhesion signatures and uncover cooperative interactions between receptor systems in a panel of cancer cell lines. Dual-color probes enable multiplexed single-cell mechanical phenotyping, and application to primary NK cells reveals dose-dependent responses to integrin modulators. These results establish a generalizable platform for site-defined AOC generation and for quantitative, high-throughput measurement of receptor-mediated adhesion dynamics.

bioengineering↗

bioRxiv2026

A Biophysical Platform for Electromechanical Stimulation of Engineered Cardiac Tissues

Human engineered cardiac tissues (ECTs) provide an in vitro model for studying human cardiac physiology and drug responses, but their performance remains limited by culture systems that do not fully reproduce the heart's electrical and mechanical environment. Electrical stimulation (ES) and mechanical stimulation (MS) have each been used to improve ECT function. Their combination, referred to as electromechanical stimulation (ES+MS), can provide further benefits. However, ES+MS depends not only on the presence of both cues but also on how they are coordinated in time. Here, we developed an incubator-compatible biophysical platform that delivers ES and MS independently or in combination, with programmable control over timing, amplitude, frequency, duration, and waveform. Calibration and dynamic characterization demonstrated tissue-relevant strain delivery, rapid and repeatable motion, and minimal attenuation and timing lag at the designated frequency of 1.5 Hz. We then compared four 6 h conditioning regimens: unstimulated control, ES alone, unsynchronized ES+MS, and synchronized ES+MS. We hypothesized that the synchronized ES+MS group, in which electrical excitation was aligned with peak externally applied strain, would produce the greatest increase in contractile force. Consistent with this hypothesis, synchronized ES+MS increased normalized twitch force by approximately 44% on average, whereas the other groups showed no comparable improvement. Twitch-timing metrics did not exhibit coordinated enhancement after 6 h, suggesting that the force increase reflects an adaptive biomechanical response rather than broad tissue maturation. These findings identify ES-MS timing as an important design parameter for ECT conditioning.

bioengineering↗

bioRxiv2026

Elevated hydrostatic pressure modulates endothelial junctional mechanotransduction through VE-cadherin remodelling and altered association with YAP1, EPS8: an endothelium-on-chip study

Endothelial dysfunction is a hallmark of numerous vascular pathologies and is strongly influenced by mechanobiological forces within the vascular microenvironment. While the effects of shear stress have been extensively investigated, the mechanisms by which elevated hydrostatic pressure regulates endothelial junctional organisation remain sparsely investigated. Here, we employed a microfluidic platform to investigate the combined effects of low shear stress (1.4 dyne/cm2) and elevated hydrostatic pressure (~3972 Pa) on endothelial junctional dynamics. Elevated hydrostatic pressure induced marked remodelling of VE-cadherin junctions, characterised by formation of serrated, finger-like structures accompanied by increased YAP1 nuclear localisation and reduced YAP1-VE-cadherin cytoplasmic colocalisation compared to shear stress alone conditions. Further, elevated hydrostatic pressure also demonstrated an increase in cytoplasmic accumulation of EPS8, an actin adaptor protein, and increased cytoplasmic EPS8-VE-cadherin colocalisation. These observations were accompanied by functional changes marked by increased endothelial permeability, and enhanced THP-1 monocyte adhesion, thus suggesting activation of mechanosensitive pathways linked to dynamic junctional reorganisation. Inhibition of PI3K at elevated hydrostatic pressure exhibited a thin VE-cadherin patterning and increased cytoplasmic EPS8-VE-cadherin colocalisation, thus demonstrating a prominent role for PI3K signalling in regulating the junction organisation. Interestingly, Piezo-1 activation using Yoda1 produced context-dependent effects. Under shear stress alone, Yoda1 promoted YAP1 nuclear translocation, reduced YAP1-VE-cadherin colocalisation, increased endothelial permeability but strikingly did not impact THP-1 adhesion compared to shear stress alone conditions. In contrast, under elevated hydrostatic pressure conditions, Yoda1 significantly reduced both endothelial permeability and THP-1 adhesion while increasing YAP1-VE-cadherin colocalisation and decreasing YAP1 nuclear accumulation. Collectively, these findings identify a previously underappreciated elevated hydrostatic pressure-Piezo-1-PI3K signalling axis that regulates endothelial barrier integrity and pro-adhesive endothelial activation through coordinated regulation of VE-cadherin, YAP1, and EPS8. These results highlight elevated hydrostatic pressure as a unique mechanobiological stimulus, distinct from that of shear stress alone and provide novel insights into mechanisms underlying microvascular dysfunction.

bioengineering↗

bioRxiv2026

Embedding wear assessment in musculoskeletal simulation: A proof-of-concept application to total hip arthroplasty

Predicting wear in artificial joints requires integrating joint dynamics, contact mechanics and progressive surface evolution, yet these processes are often treated separately. In total hip arthroplasty (THA), finite-element approaches remain the reference standard, but they are computationally demanding and usually rely on boundary conditions from independent musculoskeletal (MSK) models, hindering consistent coupling and feedback between wear progression and movement dynamics. As a single-subject proof of concept, we present a computational framework that embeds wear estimation within forward MSK simulations through OpenSim-MATLAB integration. Contact variables are computed using an elastic-foundation formulation, and wear is updated through the Archard law, enabling cyclic prediction of contact mechanics and surface evolution within a single workflow at practical computational cost. The framework was evaluated in one subject with right THA during five activities of daily living and numerically benchmarked against finite-element simulations. A long-term walking analysis of 4 million cycles was also performed to assess geometry updating. Across tasks, peak contact pressures remained within 7% of finite-element predictions. Linear wear depth and volumetric loss showed maximum deviations of 16% and 13%, respectively. Accounting for progressive geometry changes yielded a maximum wear depth about 31% lower than linear extrapolation. These preliminary results support the framework's computational feasibility and numerical consistency for the tested case; nevertheless, multi-subject evaluation is required before broader predictive or clinical use.

bioengineering↗