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VirtuousPocketome: A Computational Tool for Screening Protein-ligand Complexes to Identify Similar Binding Sites bioRxiv. Bioeng. Pub Date : 2024-03-18 Lorenzo Pallante, Marco Cannariato, Lampros Androutsos, Eric Adriano Zizzi, Agorakis Bompotas, Xhesika Hada, Gianvito Grasso, Athanasios Kalogeras, Seferina Mavroudi, Giacomo Di Benedetto, Konstantinos Theofilatos, Marco Agostino Deriu
Protein residues within binding pockets play a critical role in determining the range of ligands that can interact with a protein, influencing its structure and function. Identifying structural similarities in proteins offers valuable insights into their function and activation mechanisms, aiding in predicting protein-ligand interactions, anticipating off-target effects, and facilitating the development
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Evaluating Paraspinal Muscle Response and Compensation via Musculoskeletal Modeling in Spinal Stenosis Surgeries bioRxiv. Bioeng. Pub Date : 2024-03-17 Ryan Jones, Yogesh Kumaran, Adit Padgaonkar, Brett Hoffman, Kyle Behrens, Hossen Elgafy, Sudharshan Tripathi, Vijay K Goel
Introduction: Lumbar spinal stenosis is a common cause of lower back pain and weakness in elderly patients. The gold standard treatment for this is lumbar laminectomy which involves widespread muscle damage to the multifidus, a complete loss of the posterior tension band which contains the supraspinous and interspinous ligaments. However, in recent years minimally invasive techniques such as bilateral
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D2Sim: A Computational Simulator for Nanopore Sequencing based DNA Data Storage bioRxiv. Bioeng. Pub Date : 2024-03-17 subhasiny Sankar, Wang Yixin, Md Noor-A-Rahim, Erry Gunawan, Yong Liang Guan, Chueh Loo Poh
DNA data storage has gained significant attention due to its high storage density and durability. However, errors during storage and reading processes compromise data integrity, prompting research into error correction strategies. Researchers have been exploring physical redundancy (data copies) and logical redundancy (added redundancy in error-correcting codes) to mitigate errors. Evaluating these
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High-frequency extracellular spiking in electrically-active cancer cells bioRxiv. Bioeng. Pub Date : 2024-03-17 Rustamzhon Melikov, Francesco De Angelis, Rosalia Moreddu
Microelectrode matrices have been extensively used in the past 30 years as a reliable platform to record the extracellular activity of cells traditionally regarded to as excitable, i.e. brain cells and muscle cells. Meanwhile, fundamental biology studies on cancer cells since the 1970s reveal that they exhibit altered functionalities of ion channels, membrane potentials, metabolism, and communication
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Biomimetic fractal topography enhances podocyte maturation in vitro bioRxiv. Bioeng. Pub Date : 2024-03-17 Chuan Liu, Praful Aggarwal, Karl T. Wagner, Shira S. Landau, Teng Cui, Xin Song, Laleh Shamaei, Naimeh Rafatian, Yimu Zhao, Sonia Rodriguez-Ramirez, Keith Morton, Elizabeth Virlee, Chen Yu Li, Dawn Bannerman, Simon Pascual-Gil, Sargol Okhovatian, Anastasia Radisic, Sergi Clotet-Freixas, Teodor Veres, Mohtada Sadrzadeh, Tobin Filleter, Ulrich Broeckel, Ana Konvalinka, Milica Radisic
Cells and tissues in their native environment are organized into intricate fractal structures, which are rarely recapitulated in their culture in vitro. The extent to which fractal patterns that resemble complex topography in vivo influence cell maturation, and the cellular responses to such shape stimulation remain inadequately elucidated. Yet, the application of fractal cues (topographical stimulation
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Photoelectricity generation from beet juice in a bio-electrochemical cell bioRxiv. Bioeng. Pub Date : 2024-03-17 Yaniv Shlosberg
The world is striving for the development of novel clean energy technologies that can replace the utilization of fossil fuels, and assist in the struggle against climate change. A unique approach that does not involve any carbon emission is bio-photo electrochemical cells (BPECs). This method integrates live organisms with an electrochemical system, while native redox species that exist in the organisms
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Multiscale Correlations between Joint and Tissue-Specific Biomechanics and Anatomy in Postmortem Ovine Stifles bioRxiv. Bioeng. Pub Date : 2024-03-17 Aritra Chatterjee, Zachary Robert Davis, Timothy Lescun, Deva D Chan
The stability of the knee joint is an important indicator of its overall health and function. Joint stability depends on multiple structural and functional properties that include the anatomy of the underlying bones, the geometry and stiffness of the joint capsule and the soft tissues within like tendon, ligaments, cartilage and meniscus. The multiscale biomechanical relationships between the form
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Multi-Scale Computational Model of Microvascular Remodeling in Idiopathic Pulmonary Fibrosis bioRxiv. Bioeng. Pub Date : 2024-03-17 Julie Leonard-Duke, Samuel M J Agro, David J Csordas, Anthony C Bruce, Taylor G Eggertsen, Tara N Tavakol, Thomas H Barker, Catherine A Bonham, Jeffrey J Saucerman, Lakeshia J Taite, Shayn M Peirce
In idiopathic pulmonary fibrosis (IPF), progressive extracellular matrix (ECM) stiffening and dysregulated levels of growth factors, such as vascular endothelial growth factor A (VEGF-A), disrupt endothelial cell (EC) to pericyte cell communication. The physical coupling of ECs with pericytes in the microcirculation is necessary for maintaining microvessel homeostasis and function, and their uncoupling
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MAGNETICALLY-DRIVEN HYDROGEL SURFACES FOR DYNAMIC STIFFNESS MODULATION FOR MODULATING MACROPHAGE BEHAVIOR bioRxiv. Bioeng. Pub Date : 2024-03-17 Lanhui Li, Els Alsema, Nick Beijer, Burcu Gumuscu
During the host response towards implanted biomaterials, macrophages can shift phenotype rapidly upon changes in their microenvironment within the host tissue. Exploration of this phenomenon can gain significantly from the development of adequate tools. Creating dynamic surface alterations on classical hydrogel substrates presents challenges, particularly when integrating them with cell cultivation
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Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain bioRxiv. Bioeng. Pub Date : 2024-03-16 Ya-Hui Lin, Li-Wen Wang, Yen-Hui Chen, Yi-Chieh Chan, Shang-Hsiu Hu, Sheng-Yan Wu, Chi-Shiun Chiang, Guan-Jie Huang, Shang-Da Yang, Shi-Wei Chu, Kuo-Chuan Wang, Chin-Hsien Lin, Pei-Hsin Huang, Hwai-Jong Cheng, Bi-Chang Chen, Li-An Chu
Tissue clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling
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BMP2 binds non-specifically to PEG-passivated biomaterials and induces substantial signaling bioRxiv. Bioeng. Pub Date : 2024-03-16 Jean Le Pennec, Amaury Guibert, Romain R Vives, Elisa Migliorini
Biomaterials are widely employed across diverse biomedical applications and represent an attractive strategy to explore physiologically how extracellular matrix components influence the cellular response. In this study, we aimed to use previously developed biomimetic streptavidin platforms to investigate the role of glycosaminoglycans (GAGs) in bone morphogenetic protein 2 (BMP2) signaling. However
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In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention bioRxiv. Bioeng. Pub Date : 2024-03-16 Natalie Jasiewicz, Kuo-Ching Mei, Hannah Oh, Emily Bonacquisti, Ameya Chaudhari, Camryn Byrum, Brian Jensen, Juliane Nguyen
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction, but their therapeutic efficacy is limited by inefficient accumulation at the target site. A non-invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here we show that EVs decorated
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High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics bioRxiv. Bioeng. Pub Date : 2024-03-16 Kaiyuan Tang, Xiaoyu Zhou, Shao-Yu Fang, Erica Vandenbulcke, Andrew Du, Johanna Shen, Hanbing Cao, Jerry Zhou, Krista Chen, Shan Xin, Liqun Zhou, Shawn H Lin, Medha Majety, Xingyu Ling, Stanley Z Lam, Ryan Chow, Suxia Bai, Timothy Nottoli, Carmen Booth, Chen Liu, Matthew B Dong, Sidi Chen
The advancement of CRISPR gene editing technology, especially the development of Cas9 knock-in mice, has significantly boosted the functional discovery of various genetics factors in diverse fields including genetics, genomics, immunology, and the biology of cancer. However, the pleiotropic effects on human disease and the complex nature of gene interaction networks require a knock-in mouse model capable
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Microbiome single cell atlases generated with a commercial instrument bioRxiv. Bioeng. Pub Date : 2024-03-16 Xiangpeng Li, Linfeng Xu, Benjamin Demaree, Cecilia Noecker, Jordan E. Bisanz, Daniel W. Weisgerber, Cyrus Modavi, Peter J. Turnbaugh, Adam R. Abate
Single cell sequencing is useful for resolving complex systems into their composite cell types and computationally mining them for unique features that are masked in pooled sequencing. However, while commercial instruments have made single cell analysis widespread for mammalian cells, analogous tools for microbes are limited. Here, we present EASi-seq (Easily Accessible Single microbe sequencing).
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WISH-BONE: Whole-mount In Situ Histology, to label osteocyte mRNA and protein in 3D adult mouse bones bioRxiv. Bioeng. Pub Date : 2024-03-15 Quentin A Meslier, Timothy J. Duerr, Brian Nguyen, James R Monaghan, Sandra J. Shefelbine
Bone is a three dimensional and highly dynamic tissue under constant remodeling. Commonly used tools to investigate bone biology require sample digestion for biomolecule extraction or only provide two-dimensional spatial information. There is a need for 3D tools to investigate spatially preserved biomarker expression in osteocytes. In this work, we present a new method, WISH-BONE, to label osteocyte
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Modeling the impact of optimized airflow and sick pen management on the spread of infectious diseases in swine barns bioRxiv. Bioeng. Pub Date : 2024-03-15 Maryam Safari, Christian Fleming, Jason Ardila Galvis, Aniruddha Deka, Felipe Sanchez, Gustavo Machado, Chi-An Yeh
The airborne spread of infectious livestock diseases plays a crucial role in the propagation of epidemics, particularly in populations confined to densely populated facilities, such as commercial swine barns. Therefore, quantitative assessments for the performance of barn ventilation systems may serve as an alternative biocontainment control strategy to reduce the spread of infectious pathogens. In
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Intra-Lymph Node Crosslinking of Antigen-Bearing Polymers Enhances Humoral Immunity and Dendritic Cell Activation bioRxiv. Bioeng. Pub Date : 2024-03-15 Erin M Euliano, Anushka Agrawal, Marina H Yu, Tyler P Graf, Emily M Henrich, Alyssa A Kunkel, Kevin J McHugh
Lymph node (LN)-resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen-presenting capabilities and proximity to a high concentration of immune cells. Direct intra-LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection but is infeasible to implement clinically. Employing the
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A sensorimotor enhanced neuromusculoskeletal model for simulating postural control of upright standing bioRxiv. Bioeng. Pub Date : 2024-03-15 Julian Shanbhag, Sophie Fleischmann, Iris Wechsler, Heiko Gassner, Jürgen Winkler, Bjoern M Eskofier, Anne D Koelewijn, Sandro Wartzack, Jörg Miehling
The human's upright standing is a complex control process that is not yet fully understood. Postural control models can provide insights into the body's internal control processes of balance behaviour. Using physiologically plausible models can also help explaining pathophysiological motion behaviour. In this paper, we introduce a neuromusculoskeletal postural control model using sensor feedback consisting
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CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under control of antigen sensing in microwell arrays bioRxiv. Bioeng. Pub Date : 2024-03-15 Youngbin Cho, Matthew Laird, Teddi Bishop, Ruxuan Li, Elisa Ruffo, Jason Lohmueller, Ioannis K Zervantonakis
The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D tumor spheroids and determine
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Whole protein sequencing and quantification without proteolysis, terminal residue cleavage, or purification: A computational model bioRxiv. Bioeng. Pub Date : 2024-03-14 G Sampath
Sequencing and quantification of whole proteins in a sample without separation, terminal residue cleavage, or proteolysis are modeled computationally. Similar to recent work on DNA sequencing (PNAS 113, 5233-5238, 2016), a high-volume conjugate is attached to every instance of amino acid (AA) type AAi, 1 ≤ i ≤ 20, in an unfolded whole protein, which is then translocated through a nanopore. From the
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Electrochemical Biosensor Using Polymer Nanocomposites for G6PD Deficiency Detection bioRxiv. Bioeng. Pub Date : 2024-03-14 Ronald Rastre Salas, Marcos Marques da Silva Paula, Yonny Romaguera Bracelay, Walter Brito
Electrochemical biosensors based on the combination of DHP, OG, AuNPs, and G6PD, used to determine the enzymatic activity of G6PD, showed optimal current intensity values close to pH 7.8 at room temperature. Square wave voltammetry was optimized and used to evaluate the responses of the biosensors during the enzymatic reaction and construct the analytical curves. The best results were found under the
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Direct Ink Writing of Graphene Oxide Reinforced 13-93B1 Bioactive Glass Scaffolds for Bone Tissue Engineering Applications bioRxiv. Bioeng. Pub Date : 2024-03-14 Kartikeya Dixit, Ashok Vishwakarma, Hitendra Kumar, Keekyoung Kim, Niraj Sinha
Graphene-reinforced bioactive glass scaffolds have gained significant attention in the field of bone tissue engineering due to their unique combination of mechanical strength, bioactivity, and electrical conductivity. Additive manufacturing techniques, such as 3D printing, provide a versatile platform for fabricating these scaffolds with precise control over their architecture and composition. Consequently
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Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product bioRxiv. Bioeng. Pub Date : 2024-03-14 Avanish Mishra, Shih-Bo Huang, Taronish Dubash, Risa Burr, Ben S. Wittner, Quinn E. Cunneely, Victor R. Putaturo, Akansha Deshpande, Ezgi Antmen, Kaustav A. Gopinathan, Keisuke Otani, Yoshiyuki Miyazawa, Ji Eun Kwak, Sara Y. Guay, Justin Kelly, John Walsh, Linda Nieman, Isabella Galler, PuiYee Chan, Michael S. Lawrence, Ryan J. Sullivan, Aditya Bardia, Douglas S. Micalizzi, Lecia V. Sequist, Richard
Circulating Tumor Cells (CTCs), interrogated by sampling blood from patients with cancer, contain multiple analytes, including intact RNA, high molecular weight DNA, proteins, and metabolic markers. However, the clinical utility of tumor cell-based liquid biopsy has been limited since CTCs are very rare, and current technologies cannot process the blood volumes required to isolate a sufficient number
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Programmable marine bacteria catalyze the valorization of lignin monomers bioRxiv. Bioeng. Pub Date : 2024-03-14 Ying Wei, Shu-Guang Wang, Peng-Fei Xia
Efficiently converting lignin, the second most abundant biopolymer on Earth, into valuable chemicals is pivotal for a circular economy and net-zero future. However, lignin is recalcitrant to bio-upcycling, demanding innovative solutions. We report here the biological valorization of lignin-derived aromatic carbon to value-added chemicals without requesting extra organic carbon and freshwater via reprogramming
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Cervical collagen network porosity assessed by SHG endomicroscopy distinguishes preterm and normal pregnancy - a pilot study bioRxiv. Bioeng. Pub Date : 2024-03-14 Wenxuan Liang, Yuehan Liu, Honghua Guan, Vorada Sakulsaengprapha, Katherine Luby-Phelps, Mala Mahendroo, Xingde Li
Background: Preterm birth (PTB) is a global public health issue affecting millions of newborns every year. Orchestrated remodeling of the cervix is essential for normal pregnancy and birth, while PTB is closely related with premature cervical ripening and loss of cervical mechanical strength. The structure and organization of fibrillar collagen in the extracellular matrix are of vital importance to
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Neural Networks Estimate Muscle Force in Dynamic Conditions Better than Hill-type Muscle Models bioRxiv. Bioeng. Pub Date : 2024-03-14 Maria Eleni Athanasiadou, Monica A. Daley, Anne D. Koelewijn
Hill-type muscle models are widely used, even though they do not accurately represent certain muscle mechanics. We explored neural networks to develop new muscle models. We trained neural networks to estimate muscle force from activation, muscle length, and muscle velocity. Training data was recorded using sonomicrometry, electromyography, and a tendon buckle on two muscles of guinea fowl. First, we
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Non-invasive laser speckle imaging of extra-embryonic blood vessels in intact few-days-old avian eggs bioRxiv. Bioeng. Pub Date : 2024-03-14 Zhenyu Dong, Simon Mahler, Carol Readhead, Xi Chen, Maya Dickson, Marianne E Bronner, Changhuei Yang
Imaging blood vessels in early-stage avian embryos has a wide range of practical applications for developmental biology studies, drug and vaccine testing, and early sex determination. Optical imaging such as brightfield transmission imaging offers a compelling solution due to its safe non-ionizing radiation, and operational benefits. However, it comes with challenges such as eggshell opacity and light
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In-Space Fabrication of Janus Base Nano-Matrix for Improved Assembly and Bioactivities bioRxiv. Bioeng. Pub Date : 2024-03-14 Anne Yau, Maxwell Landolina, Mari Anne Snow, Pinar Mesci, Brandon Williams, Jay B Hoying, Derek Duflo, Honglu Wu, Jana Stoudemire, Rose Hernandez, Yupeng Chen
In-space manufacturing of nanomaterials is a promising concept while having limited successful examples. DNA-inspired Janus base nanomaterials (JBNs), used for therapeutics delivery and tissue regeneration, are fabricated via a controlled self-assembly process in water at ambient temperature, making them highly suitable for in-space manufacturing. For the first time, we designed and accomplished the
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Dynamic culture of cerebral organoids using a pillar/perfusion plate for the assessment of developmental neurotoxicity bioRxiv. Bioeng. Pub Date : 2024-03-13 Prabha Acharya, Sunil Shrestha, Pranav Joshi, Na Young Choi, Vinod Kumar Reddy Lekkala, Soo-Yeon Kang, Gabriel Ni, Moo-Yeal Lee
Despite the potential toxicity of commercial chemicals to the development of the nervous system (known as developmental neurotoxicity or DNT), conventional in vitro cell models have primarily been employed for the assessment of acute neuronal toxicity. On the other hand, animal models used for the assessment of DNT are not physiologically relevant due to the heterogenic difference between humans and
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Reproducible generation of human liver organoids (HLOs) on a pillar plate platform via microarray 3D bioprinting bioRxiv. Bioeng. Pub Date : 2024-03-13 Sunil Shrestha, Vinod Kumar Reddy Lekkala, Prabha Acharya, Soo-Yeon Kang, Manav Goud Vanga, Moo-Yeal Lee
Human liver organoids (HLOs) hold significant potential for recapitulating the architecture and function of liver tissues in vivo. However, conventional culture methods of HLOs, forming Matrigel domes in 6-/24-well plates, have technical limitations such as high cost and low throughput in organoid-based assays for predictive assessment of compounds in clinical and pharmacological lab settings. To address
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A Machine Learning-based approach for Simultaneous Electrochemical Detection of Interfering Analytes bioRxiv. Bioeng. Pub Date : 2024-03-13 Ritwik Jain, Srishti Verma, Gorachand Dutta
Electrochemical biosensors can be used to detect analytes of importance precisely. These sensors generate rapid and accurate electrical signals that reveal the presence and concentration of the targeted analyte. Detecting multiple analytes simultaneously with an electrochemical biosensor is advantageous. It provides cost and time efficiency, multiplexing capability, and flexibility, making it valuable
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Wild lytic bacteriophages: a potential enhancer of disinfectants’ biofilm inhibition in bio-industrial settings for fruit fly production. bioRxiv. Bioeng. Pub Date : 2024-03-13 Julio Roberto Matute Torres, Mariandrée Linares Fernández, Pedro Rendón, Pamela Marie Pennington
The pathogenic nature of Morganella morganii to fruit flies has been described earlier; its biofilm prevents the larvae of mass reared fruit flies from proceeding to their next life stage by trapping them in their polymeric matrix. For the Mediterranean (Ceratitis capitata) fruit fly (“medfly”) mass rearing plants, this can be problem, due to losses generated in the production process. The presence
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Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells bioRxiv. Bioeng. Pub Date : 2024-03-13 Monica L. Ohnsorg, Kayla M. Mash, Alex Khang, Varsha V. Rao, Bruce E. Kirkpatrick, Kaustav Bera, Kristi S Anseth
The nonlinear elasticity of many tissue-specific extracellular matrices is difficult to recapitulate without the use of fibrous architectures, which couple strain-stiffening with stress relaxation. Herein, bottlebrush polymers are synthesized and crosslinked to form poly(ethylene glycol)-based hydrogels and used to study how strain-stiffening behavior affects human mesenchymal stromal cells (hMSCs)
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Local FK506 delivery induces osteogenesis in in vivo rat bone defect and rabbit spine fusion models bioRxiv. Bioeng. Pub Date : 2024-03-13 Julia Andraca Harrer, Travis M Fulton, Sreedhara Sangadala, Jarred Kaiser, Emily J Devereaux, Colleen Oliver, Steven M Presciutti, Scott D Boden, Nick J Willett
Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have
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Transcranial Functional Ultrasound Imaging Detects Focused Ultrasound Neuromodulation Induced Hemodynamic Changes in Mouse and Nonhuman Primate Brains In Vivo bioRxiv. Bioeng. Pub Date : 2024-03-12 Aurup Christian, Jonas Bendig, Samuel G. Blackman, Erica P. McCune, Sua Bae, Sergio Jimenez-Gambin, Robin Ji, Elisa E. Konofagou
Focused ultrasound (FUS) is an emerging noinvasive technique for neuromodulation in the central nervous system (CNS). To evaluate the effects of FUS-induced neuromodulation, many studies used behavioral changes, functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). However, behavioral readouts are often not easily mapped to specific brain activity, EEG has low spatial resolution
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Inter-modality source coupling: a fully- automated whole-brain data-driven structure- function fingerprint shows replicable links to reading in a large-scale (N~8K) analysis bioRxiv. Bioeng. Pub Date : 2024-03-12 Aline Kotoski, Jingyu Liu, Robin Morris, Vince Calhoun
Objective: Both structural and functional brain changes have been individually associated with developing cognitive processes such as reading. However, there is limited research about the combined influence of resting-state functional and structural magnetic resonance imaging (rs-fMRI and sMRI) features in reading development, which could provide insights into the interplay between brain structure
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A cryopreservation strategy for myoblast storage in paper-based scaffolds for inter-laboratory studies of skeletal muscle health bioRxiv. Bioeng. Pub Date : 2024-03-12 Saif Rjaibi, Erik Jacques, Caroline Ni, Bin Xu, Sonya Kouthouridis, Julie Sitolle, heta Lad, Nitya Gulati, Nancy T Li, Henry Ahn, Howard Ginsberg, Boyang Zhang, Fabien Le-Grand, Penney M Gilbert, Alison P McGuigan
Three-dimensional tissue-engineered models are poised to facilitate understanding of skeletal muscle pathophysiology and identify novel therapeutic agents to improve muscle health. Adopting these culture models within the broader biology community is a challenge as many models involve complex methodologies and significant investments of time and resources to optimize manufacturing protocols. To alleviate
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Enhancing viscosity control in antibody formulations: A framework for the biophysical screening of mutations targeting solvent-accessible hydrophobic and electrostatic patches bioRxiv. Bioeng. Pub Date : 2024-03-12 Georgina B Armstrong, Vidhi Shah, Paula Sanches, Mitul Patel, Ricky Casey, Craig J Jamieson, Glenn A Burley, William J Lewis, Zahra Rattray
The formulation of high-concentration monoclonal antibody (mAb) solutions in low dose volumes for autoinjector devices poses challenges in manufacturability and patient administration due to elevated solution viscosity. In the current study, we present a systematic experimental framework for the computational screening of molecular descriptors to guide the design of mutants with modified viscosity
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An engineered human cardiac tissue model reveals contributions of systemic lupus erythematosus autoantibodies to myocardial injury bioRxiv. Bioeng. Pub Date : 2024-03-12 Sharon Fleischer, Trevor R Nash, Manuel A Tamargo, Roberta I Lock, Gabriela Venturini, Margaretha Morsink, Vanessa Li, Morgan J Lamberti, Pamela L Graney, Martin Liberman, Youngbin Kim, Richard Z Zhuang, Jaron Whitehead, Richard A. Friedman, Rajesh SONI, Jonathan G Seidman, Christine E Seidman, Laura Geraldino-Pardilla, Robert Winchester, Gordana Vunjak-Novakovic
Systemic lupus erythematosus (SLE) is a highly heterogenous autoimmune disease that affects multiple organs, including the heart. The mechanisms by which myocardial injury develops in SLE, however, remain poorly understood. Here we engineered human cardiac tissues and cultured them with IgG fractions containing autoantibodies from SLE patients with and without myocardial involvement. We observed unique
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Scalable Isolation of Surface-Engineered Extracellular Vesicles and Separation of Free Proteins via Tangential Flow Filtration and Size Exclusion Chromatography (TFF-SEC) bioRxiv. Bioeng. Pub Date : 2024-03-12 Yuki Kawai-Harada, Vasudha Nimmagadda, Masako Harada
Extracellular vesicles (EVs) represent small lipid bilayer structures pivotal in mediating intercellular communication via biomolecular transfer.1 Their inherent characteristics, including packaging, non-immunogenicity, and biofluid stability, position EVs as promising drug delivery vectors. However, developing clinical quality EVs requires multifaceted technological advancement. In this study, a method
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Sustained neurotrophic factor cotreatment enhances donor and host retinal ganglion cell survival in mice bioRxiv. Bioeng. Pub Date : 2024-03-12 Jonathan R Soucy, Emil Kriukov, Julia Oswald, John Masland, Chris Pernstich, Petr Baranov
Retinal ganglion cells (RGCs) lack regenerative capacity in mammals, and their degeneration in glaucoma leads to irreversible blindness. Traditional RGC transplantation has been limited by poor survival rates of transplanted cells in the hostile microenvironment of a diseased retina. Our research identifies brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as key
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Motor Hotspot Localization Based on Electroencephalography Using Convolutional Neural Network in Patients with Stroke bioRxiv. Bioeng. Pub Date : 2024-03-11 Ga-Young Choi, Jeong-Kweon Seo, Kyoung Tae Kim, Won Kee Chang, Nam-Jong Paik, Won-Seok Kim, Han-Jeong Hwang
Background: Although transcranial magnetic stimulation (TMS) is the optimal tool for identifying individual motor hotspots for transcranial electrical stimulation (tES), it requires a cumbersome procedure in which patients must visit the hospital each time and rely on expert judgment to determine the motor hotspot. Therefore, in previous study, we proposed electroencephalography (EEG)-based machine
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Harnessing alkaline-pH regulatable promoters for efficient methanol-free expression of enzymes of industrial interest in Komagataella phaffii bioRxiv. Bioeng. Pub Date : 2024-03-11 Marcel Albacar, Antonio Casamayor, Joaquin Arino
Background: The yeast Komagataella phaffii has become a very popular host for heterologous protein expression, very often based on the use of the AOX1 promoter, which becomes activated when cells are grown with methanol as a carbon source. However, the use of methanol in industrial settings is not devoid of problems, and therefore, the search for alternative expression methods has become a priority
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A model of task-level human stepping regulation yields semistable walking bioRxiv. Bioeng. Pub Date : 2024-03-11 Navendu S. Patil, Jonathan B. Dingwell, Joseph P. Cusumano
A simple lateral dynamic walker, with swing leg dynamics and three adjustable input parameters, is used to study how motor regulation affects frontal plane stepping. Motivated by experimental observations and phenomenological models, we imposed task-level multiobjective regulation targeting the walker's optimal lateral foot placement at each step. The regulator prioritizes achieving step width and
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zIncubascope: long-term quantitative imaging of multi-cellular assemblies inside an incubator bioRxiv. Bioeng. Pub Date : 2024-03-10 Anirban Jana, Naveen Mekhileri, Adeline Boyreau, Aymerick Bazin, Nadege Pujol, Kevin Alessandri, Gaelle Recher, Pierre Nassoy, Amaury Badon
Recent advances in bioengineering have made it possible to develop increasingly complex biological systems to recapitulate organ functions as closely as possible in vitro. Monitoring the assembly and growth of multi-cellular aggregates, micro-tissues or organoids and extracting quantitative information is a crucial but challenging task required to decipher the underlying morphogenetic mechanisms. We
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Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation bioRxiv. Bioeng. Pub Date : 2024-03-10 Mikala C Mueller, Yanmei Du, Lori A Walker, Chelsea M Magin
Respiratory diseases like pulmonary arterial hypertension (PAH) frequently exhibit sexual dimorphism. Female PAH patients are more susceptible to the disease but have increased survival rates. This phenomenon is known as the estrogen paradox, and the underlying mechanisms are not fully understood. During PAH progression in vivo, human pulmonary arterial adventitial fibroblasts (hPAAFs) differentiate
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A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant bioRxiv. Bioeng. Pub Date : 2024-03-09 Erin M Euliano, Brett H Pogostin, Anushka Agrawal, Marina H Yu, Tsvetelina H Baryakova, Tyler P Graf, Jeffrey D Hartgerink, Kevin J McHugh
Toll-like receptors (TLRs) recognize pathogen- and damage-associated molecular patterns and, in turn, trigger the release of cytokines and other immunostimulatory molecules. As a result, TLR agonists are increasingly being investigated as vaccine adjuvants, though many of these agonists are small molecules that quickly diffuse away from the vaccination site, limiting their co-localization with antigens
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Combining Cell-Intrinsic and -Extrinsic Resistance to HIV-1 By Engineering Hematopoietic Stem Cells for CCR5 Knockout and B Cell Secretion of Therapeutic Antibodies bioRxiv. Bioeng. Pub Date : 2024-03-09 William N. Feist, Sofia E. Luna, Kaya Ben-Efraim, Maria V. Filsinger Interrante, Nelson A. Amorin, Nicole M. Johnston, Theodora U. J. Bruun, Hana Y. Ghanim, Benjamin J. Lesch, Amanda M. Dudek, Matthew H. Porteus
Autologous transplantation of CCR5 null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment is limited because of the rarity of CCR5-null matched donors, the morbidities associated with allogeneic transplantation, and the prevalence of HIV-1 strains resistant to CCR5 knockout (KO) alone. Here, we propose a one-time therapy through autologous
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Empowering High Throughput Screening of 3D Models: Automated Dispensing of Cervical and Endometrial Cancer Cells bioRxiv. Bioeng. Pub Date : 2024-03-09 Samantha Seymour, Ines Cadena, Mackenzie Johnson, Molly Jenne, Iman Adem, Rachel Frankovic, Danielle Spence, Andrea Haddadin, Kaitlin Fogg
Purpose: Cervical and endometrial cancers pose significant challenges in women's healthcare due to their high mortality rates and limited treatment options. High throughput screening (HTS) of cervical and endometrial cancer in vitro models offer a promising avenue for drug repurposing and broadening patient treatment options. Traditional two-dimensional (2D) cell-based screenings have limited capabilities
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Precision Enhancement of CAR-NK Cells through Non-Viral Engineering and Highly Multiplexed Base Editing bioRxiv. Bioeng. Pub Date : 2024-03-08 Minjing Wang, Joshua B Krueger, Alexandria K Gilkey, Erin M Stelljes, Mitchell G Kluesner, Emily J Pomeroy, Joseph G Skeate, Nicholas J Slipek, Walker S Lahr, Patricia N Claudio Vazquez, Yueting Zhao, Ella J Eaton, Kanut Laoharawee, Beau R Webber, Branden S Moriarity
Natural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials and likely require advanced genome engineering to reach their full potential as a cancer therapeutic. Multiplex
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Development of a new genotype–phenotype linked antibody screening system bioRxiv. Bioeng. Pub Date : 2024-03-08 Takashi Watanabe, Hikaru Hata, Yoshiki Mochizuki, Fumie Yokoyama, Tomoko Hasegawa, Naveen Kumar, Tomohiro Kurosaki, Osamu Ohara, Hidehiro Fukuyama
Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: 1) screening starts only after Ig gene cloning and recombinant antibody production, and 2) the antibody is composed of paired chains, heavy and light
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Deep Plasma Proteome Profiling by Modulating Single Nanoparticle Protein Corona with Small Molecules bioRxiv. Bioeng. Pub Date : 2024-03-08 Ali Akbar Ashkarran, Hassan Gharibi, Seyed Majed Modaresi, Maryam Sayadi, Maryam Jafari, Zijin Lin, Danilo Ritz, David Kakhniashvili, Liangliang Sun, Markita P Landry, Amirata Saei Dibavar, Morteza Mahmoudi
The protein corona, a dynamic biomolecular layer that forms on nanoparticle (NP) surfaces upon exposure to biological fluids is emerging as a valuable diagnostic tool for improving plasma proteome coverage analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Here, we show that spiking small molecules, including metabolites, lipids, vitamins, and nutrients, into plasma can induce diverse
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Exploring the molecular structure of lipids in the design of artificial lipidated antifungal proteins bioRxiv. Bioeng. Pub Date : 2024-03-08 Hendra Saputra, Muhammad Safaat, Pugoh Santoso, Rie Wakabayashi, Masahiro Goto, Toki Taira, Noriho Kamiya
Fungal infections have been a concern for decades, yet effective and approved antifungal agents are limited. We re-cently developed a potential method to enhance the antifungal activity of a small chitin-binding domain (LysM) from Pteris ryukyuensis chitinase A (PrChiA) by the site-specific introduction of a palmitoyl (C16) group catalyzed by microbial transglutaminase (MTG). Herein, we attempted the
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Shear Stress Induces a Pro-Inflammatory Phenotype in Human Monocyte-Derived Macrophages bioRxiv. Bioeng. Pub Date : 2024-03-07 Elysa Jui, Griffin Kingsley, Hong Kim Pham, Kavya Singampalli, Ravi Birla, Jennifer Connell, Sundeep Keswani, Kathryn Jane Grande-Allen
Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response
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Decoding Stability and Epistasis in Human Myoglobin by Deep Mutational Scanning and Codon-level Machine Learning bioRxiv. Bioeng. Pub Date : 2024-03-06 Christoph Kueng, Olena Protsenko, Rosario Vanella, Michael Nash
Understanding the linkage between protein sequence and phenotypic expression level is crucial in biotechnology. Machine learning algorithms trained with deep mutational scanning (DMS) data have significant potential to improve this understanding and accelerate protein engineering campaigns. However, most machine learning (ML) approaches in this domain do not directly address effects of synonymous codons
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LDL-Binding IL-10 Reduces Vascular Inflammation in Atherosclerotic Mice bioRxiv. Bioeng. Pub Date : 2024-03-06 Lisa R Volpatti, Salvador Norton de Matos, Gustavo Borjas, Joseph Reda, Elyse A Watkins, Zhengjie Zhou, Mindy Nguyen, Ani Solanki, Yun Fang, Jeffrey A Hubbell
Atherosclerosis is a chronic inflammatory disease associated with the accumulation of low-density lipoprotein (LDL) in arterial walls. Higher levels of the anti-inflammatory cytokine IL-10 in serum are correlated with reduced plaque burden. However, cytokine therapies have not translated well to the clinic, partially due to their rapid clearance and pleiotropic nature. Here, we engineered IL-10 to
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Investigation of protein imprinted gelatin/N-Vinylformamide hydrogel membrane protein grafted on polyurethane bioRxiv. Bioeng. Pub Date : 2024-03-06 Otar Mikautadze, Dali Chkheidze, Temur Kotishadze, Mikheil Surguladze
Using polyurethane (PU) as the carrier, membrane protein as the template, NVinylformamide (NVF) as the monomer, and 1,4-Butanediol diglycidyl ether (BDDE) as the crosslinker, in the presence of gelatin, and initiated by ultraviolet radiation, the hydrogel PUNVF-Gelatin was prepared. The effects of monomer concentration, crosslinker concentration, and gelatin concentration on the adsorption capacity
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Integration of pH control into Chi.Bio reactors and demonstration with small-scale enzymatic poly(ethylene terephthalate) hydrolysis bioRxiv. Bioeng. Pub Date : 2024-03-06 Mackenzie CR Denton, Natasha P Murphy, Brenna Norton-Baker, Mauro Lua, Harrison Steel, Gregg T Beckham
Small-scale bioreactors that are affordable and accessible would be of major benefit to the research community. In previous work, an open-source, automated bioreactor system was designed to operate up to the 30 mL scale with online optical monitoring, stirring, and temperature control, and this system, dubbed Chi.Bio, is now commercially available at a cost that is typically 1-2 orders of magnitude
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2.5D Actuating Substrates Enable Decoupling the Mechanical and Biochemical Effects of Muscle Exercise on Motor Neurons bioRxiv. Bioeng. Pub Date : 2024-03-06 Angel Bu, Ferdows Afghah, Nicolas Castro, Maheera Bawa, Sonika Kohli, Karina Shah, Brandon Rios, Vincent Butty, Ritu Raman
Emerging in vivo evidence suggests that exercise impacts peripheral nerves, but the difficulty of isolating and studying the muscle-specific impact on motor neurons in vivo, as well as the inability to decouple the biochemical and mechanical impacts of exercise in this setting, motivate investigating this phenomenon in vitro. In this study, we show that tuning the mechanical properties of fibrin hydrogels
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Characterization of Composite Agarose-Collagen Hydrogels for Chondrocyte Culture bioRxiv. Bioeng. Pub Date : 2024-03-06 Clarisse Zigan, Claudia Benito Alston, Aritra Chatterjee, Luis Solotio, Deva D Chan
To elucidate the mechanisms of cellular mechanotransduction, it is necessary to employ biomaterials that effectively merge biofunctionality with appropriate mechanical characteristics. Agarose and collagen separately are common biopolymers used in cartilage mechanobiology and mechanotransduction studies but lack features that make them ideal for functional engineered cartilage. In this study, agarose