{"title":"Insights into the mechanobiology of cancer metastasis via microfluidic technologies.","authors":"Lanfeng Liang, Xiao Song, Hao Zhao, Chwee Teck Lim","doi":"10.1063/5.0195389","DOIUrl":"10.1063/5.0195389","url":null,"abstract":"<p><p>During cancer metastasis, cancer cells will encounter various microenvironments with diverse physical characteristics. Changes in these physical characteristics such as tension, stiffness, viscosity, compression, and fluid shear can generate biomechanical cues that affect cancer cells, dynamically influencing numerous pathophysiological mechanisms. For example, a dense extracellular matrix drives cancer cells to reorganize their cytoskeleton structures, facilitating confined migration, while this dense and restricted space also acts as a physical barrier that potentially results in nuclear rupture. Identifying these pathophysiological processes and understanding their underlying mechanobiological mechanisms can aid in the development of more effective therapeutics targeted to cancer metastasis. In this review, we outline the advances of engineering microfluidic devices <i>in vitro</i> and their role in replicating tumor microenvironment to mimic <i>in vivo</i> settings. We highlight the potential cellular mechanisms that mediate their ability to adapt to different microenvironments. Meanwhile, we also discuss some important mechanical cues that still remain challenging to replicate in current microfluidic devices in future direction. While much remains to be explored about cancer mechanobiology, we believe the developments of microfluidic devices will reveal how these physical cues impact the behaviors of cancer cells. It will be crucial in the understanding of cancer metastasis, and potentially contributing to better drug development and cancer therapy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrodynamic interaction between tumor treating fields and microtubule electrophysiological activities.","authors":"Xing Li, Kaida Liu, Haohan Fang, Zirong Liu, Yuchen Tang, Ping Dai","doi":"10.1063/5.0197900","DOIUrl":"10.1063/5.0197900","url":null,"abstract":"<p><p>Tumor treating fields (TTFields) are a type of sinusoidal alternating current electric field that has proven effective in inhibiting the reproduction of dividing tumor cells. Despite their recognized impact, the precise biophysical mechanisms underlying the unique effects of TTFields remain unknown. Many of the previous studies predominantly attribute the inhibitory effects of TTFields to mitotic disruption, with intracellular microtubules identified as crucial targets. However, this conceptual framework lacks substantiation at the mesoscopic level. This study addresses the existing gap by constructing force models for tubulin and other key subcellular structures involved in microtubule electrophysiological activities under TTFields exposure. The primary objective is to explore whether the electric force or torque exerted by TTFields significantly influences the normal structure and activities of microtubules. Initially, we examine the potential effect on the dynamic stability of microtubule structures by calculating the electric field torque on the tubulin dimer orientation. Furthermore, given the importance of electrostatics in microtubule-associated activities, such as chromosome segregation and substance transport of kinesin during mitosis, we investigate the interaction between TTFields and these electrostatic processes. Our data show that the electrodynamic effects of TTFields are most likely too weak to disrupt normal microtubule electrophysiological activities significantly. Consequently, we posit that the observed cytoskeleton destruction in mitosis is more likely attributable to non-mechanical mechanisms.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Y. Amofa, Katherine Michelle Patterson, Jessica Ortiz, Sanjay Kumar
{"title":"Dissecting TGF-β-induced glioblastoma invasion with engineered hyaluronic acid hydrogels","authors":"K. Y. Amofa, Katherine Michelle Patterson, Jessica Ortiz, Sanjay Kumar","doi":"10.1063/5.0203213","DOIUrl":"https://doi.org/10.1063/5.0203213","url":null,"abstract":"Glioma stem cells (GSCs) contribute to rapid cellular invasion in glioblastoma (GBM). Transforming growth factor-β (TGF-β) has been strongly implicated in supporting key GSC functions, including stemness, immunosuppression, and resistance. Although TGF-β is well-known as a driver of cancer invasion, how TGF-β supports the invasion of GSCs is not well understood. Progress in understanding mechanisms of TGF-β-driven invasion in GSC-derived tumors has been limited by an absence of three-dimensional (3D) culture systems that support TGF-β-stimulated invasion. Here, we show that 3D hyaluronic acid (HA) matrices can address this need. We perform bioinformatic analysis of human glioma datasets, which reveals progressive enrichment of TGF-β-related gene expression with increasingly aggressive glioma grade and GBM subtype. We then experimentally screen the invasion of a panel of human GSC spheroids through a set of 3D matrix systems, including collagen I, Matrigel, and HA, and find that only HA recapitulates TGF-β-induced invasion. We then show that GSCs differ in their ability to invade HA in a way that can be predicted from TGF-β receptor 2 expression and SMAD2 phosphorylation. GSC spheroid invasion depends strongly on the presence of RGD peptides on the HA backbone but is surprisingly independent of matrix metalloprotease degradability. Finally, we demonstrate that TGF-β stimulates invasion through SMAD-dependent signaling, consistent with recent observations that TGF-β/SMAD signals drive tumor microtube formation and invasion. Our work supports further development of HA as a matrix platform for dissecting contributions of TGF-β and other cytokines to GBM invasion and screening of cytokine-dependent invasion in human tumors.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141412643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shanil Gandhi, Xhorxhina Shaulli, J. Fock, F. Scheffold, Rodolphe Marie
{"title":"IgG and IgM differentiation in a particle-based agglutination assay by control over antigen surface density","authors":"Shanil Gandhi, Xhorxhina Shaulli, J. Fock, F. Scheffold, Rodolphe Marie","doi":"10.1063/5.0196224","DOIUrl":"https://doi.org/10.1063/5.0196224","url":null,"abstract":"Point-of-care (POC) testing offers fast and on-site diagnostics and can be crucial against many infectious diseases and in screening. One remaining challenge in serological POC testing is the quantification of immunoglobulin G (IgG) and immunoglobulin M (IgM). Quantification of IgG/IgM can be important to evaluate immunity and to discriminate recent infections from past infections and primary infections from secondary infections. POC tests such as lateral flow immunoassays allow IgG and IgM differentiation; however, a remaining limitation is their incapacity to provide quantitative results. In this work, we show how samples containing IgG or IgM can be distinguished in a nanoparticle-based agglutination biosensing assay by tuning the density of antigens on the nanoparticles' surface. We employ direct STochastic Optical Reconstruction Microscopy to quantify the accessible SARS-CoV-2 trimeric spike proteins conjugated to magnetic nanoparticles at a single-particle level and gain insight into the protein distribution provided by the conjugation procedure. Furthermore, we measure the anti-SARS-CoV-2 IgG/IgM induced agglutination using an optomagnetic readout principle. We show that particles with high antigen density have a relatively higher sensitivity toward IgM compared to IgG, whereas low antigen density provides a relatively higher sensitivity to IgG. The finding paves the way for its implementation for other agglutination-based serology tests, allowing for more accurate disease diagnosis.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decoding electroencephalographic responses to visual stimuli compatible with electrical stimulation","authors":"Simone Romeni, Laura Toni, F. Artoni, S. Micera","doi":"10.1063/5.0195680","DOIUrl":"https://doi.org/10.1063/5.0195680","url":null,"abstract":"Electrical stimulation of the visual nervous system could improve the quality of life of patients affected by acquired blindness by restoring some visual sensations, but requires careful optimization of stimulation parameters to produce useful perceptions. Neural correlates of elicited perceptions could be used for fast automatic optimization, with electroencephalography as a natural choice as it can be acquired non-invasively. Nonetheless, its low signal-to-noise ratio may hinder discrimination of similar visual patterns, preventing its use in the optimization of electrical stimulation. Our work investigates for the first time the discriminability of the electroencephalographic responses to visual stimuli compatible with electrical stimulation, employing a newly acquired dataset whose stimuli encompass the concurrent variation of several features, while neuroscience research tends to study the neural correlates of single visual features. We then performed above-chance single-trial decoding of multiple features of our newly crafted visual stimuli using relatively simple machine learning algorithms. A decoding scheme employing the information from multiple stimulus presentations was implemented, substantially improving our decoding performance, suggesting that such methods should be used systematically in future applications. The significance of the present work relies in the determination of which visual features can be decoded from electroencephalographic responses to electrical stimulation-compatible stimuli and at which granularity they can be discriminated. Our methods pave the way to using electroencephalographic correlates to optimize electrical stimulation parameters, thus increasing the effectiveness of current visual neuroprostheses.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-30eCollection Date: 2024-06-01DOI: 10.1063/5.0198382
Sabrina N Campelo, Zaid S Salameh, Julio P Arroyo, James L May, Sara O Altreuter, Jonathan Hinckley, Rafael V Davalos, John H Rossmeisl
{"title":"Burst sine wave electroporation (B-SWE) for expansive blood-brain barrier disruption and controlled non-thermal tissue ablation for neurological disease.","authors":"Sabrina N Campelo, Zaid S Salameh, Julio P Arroyo, James L May, Sara O Altreuter, Jonathan Hinckley, Rafael V Davalos, John H Rossmeisl","doi":"10.1063/5.0198382","DOIUrl":"10.1063/5.0198382","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an <i>in vivo</i> rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared. Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation. While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions. Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE's transient and controllable nature. Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE. B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silk fibroin promotes H3K9me3 expression and chromatin reorganization to regulate endothelial cell proliferation.","authors":"Kaixiang Gao, Yafan Xie, Fangning Xu, Qin Peng, Li Fu, Guixue Wang, Juhui Qiu","doi":"10.1063/5.0203858","DOIUrl":"10.1063/5.0203858","url":null,"abstract":"<p><p>Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H<sub>2</sub>O<sub>2</sub> treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-29eCollection Date: 2024-06-01DOI: 10.1063/5.0204201
Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner
{"title":"Testing mixing rules for structural and dynamical quantities in multi-component crowded protein solutions.","authors":"Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner","doi":"10.1063/5.0204201","DOIUrl":"10.1063/5.0204201","url":null,"abstract":"<p><p>Crowding effects significantly influence the phase behavior and the structural and dynamic properties of the concentrated protein mixtures present in the cytoplasm of cells or in the blood serum. This poses enormous difficulties for our theoretical understanding and our ability to predict the behavior of these systems. While the use of course grained colloid-inspired models allows us to reproduce the key physical solution properties of concentrated monodisperse solutions of individual proteins, we lack corresponding theories for complex polydisperse mixtures. Here, we test the applicability of simple mixing rules in order to predict solution properties of protein mixtures. We use binary mixtures of the well-characterized bovine eye lens proteins <i>α</i> and <i>γ<sub>B</sub></i> crystallin as model systems. Combining microrheology with static and dynamic scattering techniques and observations of the phase diagram for liquid-liquid phase separation, we show that reasonably accurate descriptions are possible for macroscopic and mesoscopic signatures, while information on the length scale of the individual protein size requires more information on cross-component interaction.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-28eCollection Date: 2024-06-01DOI: 10.1063/5.0209537
Yael Hanein, Josef Goding
{"title":"Guest Editorial: Implantable bioelectronics.","authors":"Yael Hanein, Josef Goding","doi":"10.1063/5.0209537","DOIUrl":"10.1063/5.0209537","url":null,"abstract":"<p><p>The realm of implantable bioelectronics represents a frontier in medical science, merging technology, biology, and medicine to innovate treatments that enhance, restore, or monitor physiological functions. This field has yielded devices like cochlear implants, cardiac pacemakers, deep brain stimulators, and vagus nerve stimulators, each designed to address a specific health condition, ranging from sensorineural hearing loss to chronic pain, neurological disorders, and heart rhythm irregularities. Such devices underscore the potential of bioelectronics to significantly improve patient outcomes and quality of life. Recent technological breakthroughs in materials science, nanotechnology, and microfabrication have enabled the development of more sophisticated, smaller, and biocompatible bioelectronic devices. However, the field also encounters challenges, particularly in extending the capabilities of devices such as retinal prostheses, which aim to restore vision but currently offer limited visual acuity. Research in implantable bioelectronics is highly timely, driven by an aging global population with a growing prevalence of chronic diseases that could benefit from these technologies. The convergence of societal health needs, advancing technological capabilities, and a supportive ecosystem for innovation marks this era as pivotal for bioelectronic research.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-28eCollection Date: 2024-06-01DOI: 10.1063/5.0203653
Maria Rocchi, Konstantina Papangelopoulou, Marcus Ingram, Youri Bekhuis, Guido Claessen, Piet Claus, Jan D'hooge, Dirk W Donker, Bart Meyns, Libera Fresiello
{"title":"A patient-specific echogenic soft robotic left ventricle embedded into a closed-loop cardiovascular simulator for advanced device testing.","authors":"Maria Rocchi, Konstantina Papangelopoulou, Marcus Ingram, Youri Bekhuis, Guido Claessen, Piet Claus, Jan D'hooge, Dirk W Donker, Bart Meyns, Libera Fresiello","doi":"10.1063/5.0203653","DOIUrl":"10.1063/5.0203653","url":null,"abstract":"<p><p>Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient-device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines <i>in silico</i> and <i>in vitro</i> modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an <i>in silico</i> lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with <i>in silico</i> modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}