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Differences in creep response of GBM cells migrating in confinement

International Biomechanics 2020年第1期7卷 44-57页

作者： Khan, Ishan Bui, Loan Bachoo, Robert Kim, Young-Tae Chuong, Cheng-Jen University of Texas at Arlington and University of Texas Southwestern Medical Center at Dallas Joint Graduate Program in Biomedical Engineering United States Department of Neurology & Neurotherapeutics University of Texas Southwestern Medical Center at Dallas Dallas TX United States University of Texas at Arlington Department of Bioengineering TX United States

Using a microfluidic platform to apply negative aspiration pressure (–20, –25, –30, –35 and –40 cm H2O), we compared the differences in creep responses of Glioblastoma Multiforme (GBM) cells while migrating in co... 详细信息

Using a microfluidic platform to apply negative aspiration pressure (–20, –25, –30, –35 and –40 cm H₂O), we compared the differences in creep responses of Glioblastoma Multiforme (GBM) cells while migrating in confinement and at a stationary state on a 2D substrate. Cells were either migrating in a channel of 5 x 5 μm cross-section or stationary at the entrance to the channel. In response to aspiration pressure, we found actively migrating GBM cells exhibited a higher stiffness than stationary cells. Additionally, migrating cells absorbed more energy elastically with a relatively small dissipative energy loss. At elevated negative pressure loads up to–30 cm H₂O, we observed a linear increase in elastic deformation and a higher distribution in elastic storage than energy loss, and the response plateaued at further increasing negative pressure loads. To explore the underlying cause, we carried out immuno-cytochemical studies of these cells and found a polarized actin and myosin distribution at the front and posterior ends of the migrating cells, whereas the distribution of the stationary group demonstrated no specific regional differences. These differences in creep response and cytoskeletal protein distribution demonstrate the importance of a migrating cell’s kinematic state to the mechanism of cell migration. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

关键词： actomyosin contraction Cancer cell creep glioblastoma viscoelastic properties

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Wearable Active Vibration Sensing for Mid-Activity Knee Health Assessment

Wearable Active Vibration Sensing for Mid-Activity Knee Heal...

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International Workshop on Wearable and Implantable Body Sensor Networks (BSN)

作者： Goktug C. Ozmen Christopher J. Nichols Lan Lan Emily Moise Christopher Sugino Alper Erturk Omer T. Inan School of Electrical and Computer Engineering Georgia Institute of Technology Atlanta GA USA BioEngineering Graduate Program Georgia Institute of Technology Atlanta GA USA Coulter Department of Biomedical Engineering Georgia Institute of Technology Atlanta GA USA George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology Atlanta GA USA Coulter Department of Biomedical Engineering School of Electrical and Computer Engineering Georgia Institute of Technology Atlanta GA USA

Non-invasive vibration measurements from the knee offer a convenient and affordable alternative to benchtop or biomechanics lab joint health monitoring systems. Recently, joint acoustic emissions (JAEs) measured from the knee were shown to be an indicator of knee health. However, the origin of JAEs is still not fully understood, which limits its acceptance and use by clinical experts. In this proof-of-concept study, rather than relying on the movements of the knee and corresponding frictional rubbing of internal surfaces to produce vibrations, we propose using an active vibration sensing approach with a known vibration source interrogating the knee. We aim to elucidate the linkage between knee vibration characteristics and structural changes in the joint following injuries. We measured tibial vibration responses of two participants using a laser vibrometer system to quantify the frequency band where the most repeatable tibial vibration measurement can be taken. Subsequently, a custom-designed wearable system measured mid-activity tibial vibration characteristics from four participants (five healthy knees and three knees with prior acute injury) during unloaded knee flexion-extensions. An active sensing knee health score was defined as the ratio of the changes in low- to high-frequency response during flexion-extension. Since changes in the boundary of tibia would alter low-frequency response more than high frequency response, we found that increased knee laxity with acute injuries resulted in an increased active sensing knee health score. Our findings demonstrate the potential of active vibration sensing as an interpretable, computationally inexpensive alternative to JAEs for wearable knee health assessment.

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A complete allosteric map of a GTPase switch in its native cellular network

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Cell Systems 2023年第3期14卷 237-246.e7页

作者： Mathy, Christopher J.P. Mishra, Parul Flynn, Julia M. Perica, Tina Mavor, David Bolon, Daniel N.A. Kortemme, Tanja Department of Bioengineering and Therapeutic Sciences University of California San Francisco San Francisco 94158 CA United States Quantitative Biosciences Institute University of California San Francisco San Francisco 94158 CA United States The UC Berkeley-UCSF Graduate Program in Bioengineering University of California San Francisco San Francisco 94158 CA United States Department of Biochemistry and Molecular Biotechnology University of Massachusetts Medical School Worcester 01605 MA United States Chan Zuckerberg Biohub San Francisco 94158 CA United States School of Life Sciences University of Hyderabad Telangana Hyderabad India

Allosteric regulation is central to protein function in cellular networks. A fundamental open question is whether cellular regulation of allosteric proteins occurs only at a few defined positions or at many sites distributed throughout the structure. Here, we probe the regulation of GTPases—protein switches that control signaling through regulated conformational cycling—at residue-level resolution by deep mutagenesis in the native biological network. For the GTPase Gsp1/Ran, we find that 28% of the 4,315 assayed mutations show pronounced gain-of-function responses. Twenty of the sixty positions enriched for gain-of-function mutations are outside the canonical GTPase active site switch regions. Kinetic analysis shows that these distal sites are allosterically coupled to the active site. We conclude that the GTPase switch mechanism is broadly sensitive to cellular allosteric regulation. Our systematic discovery of new regulatory sites provides a functional map to interrogate and target GTPases controlling many essential biological processes. © 2023 The Authors

关键词： allostery cellular regulation Gsp1 GTPases mutational scanning protein networks Ran

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Designing a system for forward-viewing 3D intravascular ultrasound imaging of blood flow velocity: assessing the effect of the catheter on velocity estimation in stenoses

Designing a system for forward-viewing 3D intravascular ultr...

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IEEE International Ultrasonics Symposium

作者： Saeyoung Kim Bowen Jing Brooks D. Lindsey Interdisciplinary BioEngineering Graduate Program Georgia Institute of Technology Atlanta GA USA Georgia Institute of Technology and Emory University Atlanta GA USA

ISBN: (数字)9781728154480

ISBN: (纸本)9781728154497

Wall shear stress (WSS) has been associated with development of high-risk plaque, which increases the likelihood for major adverse cardiac events. Recently, we have used a catheter-based, 3D intravascular forward-viewing ultrasound (FV US) transducer to directly estimate velocity fields in the femoral artery of a pig. Because inserting a catheter will affect the blood flow dynamics in the artery, in this work, the effects of a catheter on flow dynamics are experimentally quantified in both femoral and coronary stenotic vessels in phantoms to determine conditions in which velocity can be accurately estimated. An external linear array transducer was used to estimate velocity in the lumen at 5000 fps via a particle imaging velocimetry approach. The current study indicates that a hollow, catheter-based FV US could be used to quantify the flow dynamics surrounding stenoses with minimal flow disturbance, and thus could potentially assess elevated WSS and risk of plaque rupture.

关键词： Ultrasonic imaging Transducers Three-dimensional displays Imaging Catheters Arteries Blood flow

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Comparison Between Independent Component Analysis and Wiener-Hopf Filter Techniques for Eye Blink Removal

Comparison Between Independent Component Analysis and Wiener...

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Middle East Conference on Biomedical Engineering (MECBME)

作者： Sajedah Al-Momani Hasan Al-Nashash Hasan S. Mir Biomedical Engineering Graduate Program American University of Sharjah Sharjah UAE Biosciences and Bioengineering Research Institute American University of Sharjah Sharjah UAE

ISBN: (数字)9781728123585

ISBN: (纸本)9781728123592

Electroencephalogram (EEG) is useful in the clinical diagnosis of various brain diseases. However, the existence of artifacts corrupting the EEG reduces the ability to do such a proper diagnosis. One of these unwanted signals is the eye blink. Therefore, pre-processing of the EEG is of great importance for proper diagnosis. This work compares between using the Independent component Analysis (ICA) and the Wiener filter techniques for removing eye blink (EB) artifacts from EEG. EEG datasets contaminated with EBs are used for quantifying the performance of the EB rejection methods. Mean squared error (MSE) is calculated and compared between the two methods. The Results show that the Wiener-Hopf filter gives better results in rejecting EBs and producing artifact-free EEG signal.

关键词： Electroencephalography Wiener filters Integrated circuits Electrooculography Biomedical engineering Filtering Electrodes

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Modulation of stem cell morphology and differentiation using a mussel-inspired gelatin-based hydrogels 42

Modulation of stem cell morphology and differentiation using...

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42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence

作者： Pacelli, Settimio Modaresi, Saman Chakravarti, Aparna R. Vergel, Filippo Elmi Kurlbaum, Cecilia Fang, Madeline Castanho, Flavia Basu, Sayantani Paul., Arghya Biointel research laboratory Department of Chemical and Petroleum Engineering Bioengineering Graduate Program School of Engineering University of Kansas LawrenceKS United States

ISBN: (纸本)9781510883901

Statement of Purpose: Hydrogels represent suitable platforms that can be designed to mimic the extracellular matrix microenvironment, and control the biological response of stem cells. Precisely, physical, mechanical and superficial properties of hydrogels dictate the ability of stem cells to adhere, proliferate, and differentiate. Understanding the role of each parameter can be useful to fabricate hydrogels with a set of well-defined properties to exert a direct control over stem cells morphology, secretion of therapeutic factors, as well as gene expression [1]. © 2019 Omnipress - All rights reserved.

关键词： Stem cells

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Imaging neurotransmitter transport in live cells with stimulated Raman scattering microscopy

arXiv

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arXiv 2022年

作者： Manifold, Bryce Dorlhiac, Gabriel F. Landry, Markita P. Streets, Aaron Department of Bioengineering University of California Berkeley BerkeleyCA94720 United States Biophysics Graduate Group University of California Berkeley BerkeleyCA94720 United States Department of Chemical and Biomolecular Engineering University of California Berkeley BerkeleyCA94720 United States Innovative Genomics Institute University of California Berkeley BerkeleyCA94720 United States California Institute for Quantitative Biosciences QB3 University of California Berkeley BerkeleyCA94720 United States Chan-Zuckerberg Biohub San FranciscoCA94158 United States UC Berkeley-UC San Francisco Graduate Program in Bioengineering University of California Berkeley BerkeleyCA94720 United States

Chemical neurotransmission is central to neurotypical brain function but also implicated in a variety of psychiatric and neurodegenerative diseases. The release dynamics of neurotransmitters is correlated with but distinct from neuronal electrical signal propagation. It is therefore necessary to track neurotransmitter modulation separately from neuron electrical activity. Here, we present a new approach for imaging deuterated neurotransmitter molecules in the cell-silent window with stimulated Raman scattering (SRS) microscopy. Using SRS microscopy, we perform direct imaging of deuterated dopamine and GABA in PC12 chromaffin cells, and in primary hippocampal neurons, respectively, based on the carbon-deuterium vibrational frequencies. We demonstrate that SRS imaging of these isotopologues directly visualizes intracellular neurotransmitters without changing the neurotransmitters’ chemical identity, and requiring custom synthesis or genetic encoding protocols. We further show that stimulation of neurotransmitter release results in an overall 20-50% intracellular neurotransmitter signal reduction in agreement with comparable neurotransmission dynamics studies, with the ability to observe inter- and intracellular variation in vesicular neurotransmitter release. Taken together, our data suggest that neurotransmitter isotopologues can serve as a commercially-available, biocompatible, and generalizable method to image neurotransmitters with deuterated molecules that are virtually chemically identical to their native counterparts. © 2022, CC BY.

关键词： Stimulated Raman scattering

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Physics-driven Deep Learning for PET/MRI

arXiv

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arXiv 2022年

作者： Rajagopal, Abhejit Leynes, Andrew P. Dwork, Nicholas Scholey, Jessica E. Hope, Thomas A. Larson, Peder E.Z. Department of Radiology and Biomedical Imaging University of California San Francisco94158 United States Uc Berkeley-UCSF Joint Graduate Program in Bioengineering University of California San Francisco United States University of California BerkeleyCA United States Department of Radiation Oncology University of California San Francisco94158 United States Departments of Pediatrics and Radiology University of Colorado Anschutz 80045 United States

In this paper, we review physics- and data-driven reconstruction techniques for simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) systems, which have significant advantages for clinical imaging of cancer, neurological disorders, and heart disease. These reconstruction approaches utilize priors, either structural or statistical, together with a physics-based description of the PET system response. However, due to the nested representation of the forward problem, direct PET/MRI reconstruction is a nonlinear problem. We elucidate how a multi-faceted approach accommodates hybrid data- and physics-driven machine learning for reconstruction of 3D PET/MRI, summarizing important deep learning developments made in the last 5 years to address attenuation correction, scattering, low photon counts, and data consistency. We also describe how applications of these multi-modality approaches extend beyond PET/MRI to improving accuracy in radiation therapy planning. We conclude by discussing opportunities for extending the current state-of-the-art following the latest trends in physics- and deep learning-based computational imaging and next-generation detector hardware. Copyright © 2022, The Authors. All rights reserved.

关键词： Magnetic resonance imaging

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Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer's disease

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Cell 2025年

作者： Chen, Junchen Hadi, Fatemeh Wen, Xingzhao Zhao, Wenxin Xu, Ming Xue, Shuanghong Lin, Pei Calandrelli, Riccardo Richard, John Lalith Charles Song, Zhixuan Li, Jessica Amani, Alborz Liu, Yang Chen, Xu Zhong, Sheng Shu Chien-Gene Lay Department of Bioengineering University of California San Diego La Jolla San Diego CA United States Institute of Engineering in Medicine University of California San Diego La Jolla San Diego CA United States Program in Bioinformatics and Systems Biology University of California San Diego La Jolla San Diego CA United States School of Biological Sciences University of California San Diego La Jolla San Diego CA United States Department of Neurosciences University of California San Diego La Jolla San Diego CA United States Neuroscience Graduate Program University of California San Diego La Jolla San Diego CA United States

Virtually all individuals aged 65 or older develop at least early pathology of Alzheimer's disease (AD), yet most lack disease-causing mutations in APP, PSEN, or MAPT, and many do not carry the APOE4 risk allele. This raises questions about AD development in the general population. Although transcriptional dysregulation has not traditionally been a hallmark of AD, recent studies reveal significant epigenomic changes in late-onset AD (LOAD) patients. We show that altered expression of the LOAD biomarker phosphoglycerate dehydrogenase (PHGDH) modulates AD pathology in mice and human brain organoids independent of its enzymatic activity. PHGDH has an uncharacterized role in transcriptional regulation, promoting the transcription of inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKa) and high-mobility group box 1 (HMGB1) in astrocytes, which suppress autophagy and accelerate amyloid pathology. A blood-brain-barrier-permeable small-molecule inhibitor targeting PHGDH's transcriptional function reduces amyloid pathology and improves AD-related behavioral deficits. These findings highlight transcriptional regulation in LOAD and suggest therapeutic strategies beyond targeting familial mutations. © 2025 The Author(s)

关键词： Alzheimer's disease amyloid pathology astrocyte biomarker LOAD PHGDH small molecule therapeutic candidate transcriptional regulation

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Spinal functional Magnetic Resonance Imaging (fMRI) on Human Studies: A Literature Review

Spinal functional Magnetic Resonance Imaging (fMRI) on Human...

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2019 Advances in Science and Engineering Technology International Conferences, ASET 2019

作者： Al-Momani, Sajedah Dhou, Salam Biomedical Engineering Graduate Program American University of Sharjah Sharjah United Arab Emirates Department of Computer Science and Engineering Biomedical Engineering Graduate Program Biosciences and Bioengineering Research Institute American University of Sharjah Sharjah United Arab Emirates

ISBN: (纸本)9781538682715

Spinal functional Magnetic Resonance Imaging (fMRI) is a newly emerging non-invasive imaging technique that has been introduced to study the Blood Oxygenation Level Dependent (BOLD) changes in the spinal cord associated with a certain activity or even at rest. Spinal fMRI is also used to assess the treatment of many dysfunctions affect the spinal cord such as spinal cord injury (SCI) and Multiple sclerosis (MS). The purpose of this paper is to propose a literature review of spinal fMRI studies performed on healthy human volunteers. The studies reviewed are divided based on the paradigm being performed during image acquisition into (1) studies under activities and stimulus which are further classified according to the type of the stimuli, and (2) studies at resting state. Moreover, the limitations of spinal fMRI and how to tackle them are discussed. © 2019 IEEE.

关键词： Magnetic resonance imaging

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