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A physical picture of liquid–liquid phase separation of proteins

Journal of Molecular Liquids 2025年 424卷

作者： Kinoshita, Masahiro Hayashi, Tomohiko Nakamura, Yuka Yoshimori, Akira Katahira, Masato Nagata, Takashi Department of Chemistry of Science Chiba University 1-33 Yayoi-cho Inage Chiba263-8522 Japan Institute of Advanced Energy Kyoto University Kyoto Uji611-0011 Japan Interdisciplinary Program of Biomedical Engineering Assistive Technology and Art and Sports Sciences Faculty of Engineering Niigata University 8050 Ikarashi 2-no-cho Nishi-ku Niigata950-2181 Japan Department of Physics Niigata University Niigata950-2181 Japan

Liquid-liquid phase separation (LLPS) of proteins, by which they assemble and partition into a protein-dense phase and a protein-dilute phase, has caught much attention due to its essential roles in a variety of biological processes. Nevertheless, its mechanism remains to be unveiled. Here we develop a physical picture covering almost all the aspects of LLPSs of diverse systems. In our view, when only the proteins are looked at, one of the two phases is liquid-like and the other is gas-like. We relate LLPS to gas–liquid phase separation (GLPS) of simple fluids wherein the pivotal quantity is kBT (kB is the Boltzmann constant and T is the absolute temperature) divided by the absolute value of the minimum of interaction potential between fluid particles. GLPS occurs only if the pivotal quantity is sufficiently small. For LLPS, the interaction potential must be replaced by the potential of mean force (PMF) between protein molecules in aqueous solution. We do not explicitly consider aqueous solution, and its influence on properties of protein molecules is incorporated in PMF. PMF can reach its deep minimum when the two protein molecules associate. A physical interpretation is given for GLPS from a statistical-mechanics point of view, and it is extended to LLPS. In the extension, we discuss not only the similarities between the two phase separations but also the physical factors to be taken into account only in LLPS due to the fact that proteins are large molecules possessing polyatomic structures and they are immersed in aqueous solution. LLPS can be categorized as a biological self-assembly process. By reconsidering the results obtained in our earlier studies on biological self-assembly processes, we specify the entropic and energetic factors driving or opposing coacervation (association) of protein molecules followed by LLPS. We clarify the differences between LLPSs of folded proteins (i.e., proteins in the native states) and intrinsically disordered proteins. There c

关键词： Alkali halides

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Protocol to characterize longitudinal gut motility in mice using transit time, tissue harvest, and whole-mount immunostaining

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STAR Protocols 2025年第2期6卷 103761页

作者： Frith, Mary E. Kashyap, Purna C. Linden, David R. Chang, Eugene B. Interdisciplinary Scientist Training Program University of Chicago Chicago 60637 IL United States Department of Medicine University of Chicago Chicago 60637 IL United States Division of Gastroenterology and Hepatology Department of Medicine Mayo Clinic Rochester 55905 MN United States Enteric Neuroscience Program Department of Physiology and Biomedical Engineering Mayo Clinic Rochester 55905 MN United States

Transit time is a key in vivo metric of gastrointestinal (GI) motility, which is a physiologic readout of cellular communication within the enteric system. Here, we present a protocol to characterize longitudinal gut motility in mice. We describe steps for transit testing, whole-mount immunostaining, and tissue harvest. We then detail procedures for image processing and manual cell counting. This protocol seeks to minimize inter-trial variability while assessing cellular and molecular features that may underpin motility differences between experimental conditions. For complete details on the use and execution of this protocol, please refer to Frith et al.¹ © 2025 The Authors

关键词： Metabolism Model Organisms Systems biology

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PC-based tele-audiometry

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TELEMEDICINE JOURNAL AND E-HEALTH 2007年第5期13卷 501-508页

作者： Choi, Jong Min Lee, Haet Bit Park, Cheol Soo Oh, Seung Ha Park, Kwang Suk Interdisciplinary Program for Biomedical Engineering College of Medicine Seoul National University Seoul Republic of Korea. Telemedicine Association

A personal computer (PC)-based audiometer was developed for interactive remote audiometry. This paper describes a tele-audiometric system and evaluates the performance of the device when compared with conventional face-to-face audiometry. The tele-audiometric system is fully PC-based. A sound card featuring a high-quality digital-to-analog converter is used as a pure- tone generator. The audiometric programs were developed based on Microsoft Windows in order to maximize usability. Audiologists and their subjects can use the tele- audiometry system as one would utilize any PC application. A calibration procedure has been applied for the standardization of sound levels in the remote system. The performance of this system was evaluated by comparing PC-based audiometry with the conventional clinical audiometry system for 37 subjects. Also, performance of the PC-based system was evaluated during use at a remote site. The PC-based audiometry system estimated the audiometric threshold with an error of less than 2.3 dBSPL. Only 10.7% of the results exhibited an error greater than 5 dBSPL during use at a remote site. The PC-based tele-audiomerty showed acceptable results for use at a remote site. This PC- based system can be used effectively and easily in many locations that have Internet access but no local audiologists.

关键词： AUDIOMETRY TELECOMMUNICATION in medicine MEDICAL informatics MEDICAL care -- Computer network resources

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Chondrogenic and chondroprotective response of composite collagen I/II-hyaluronic acid scaffolds within an inflammatory osteoarthritic environment

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Biomaterials Science 2025年 2025 May 12页

作者： Battistoni, Carly M. Munoz Briones, Javier Brubaker, Douglas K. Panitch, Alyssa Liu, Julie C. Davidson School of Chemical Engineering Purdue University West LafayetteIN47907 United States Weldon School of Biomedical Engineering Purdue University West LafayetteIN47907 United States Purdue Interdisciplinary Life Science Program Purdue University West LafayetteIN47907 United States Center for Global Health and Diseases Department of Pathology Case Western Reserve University ClevelandOH44016 United States Blood Heart Lung Immunology Research Center University Hospitals ClevelandOH44106 United States Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University AtlantaGA30332 United States

Inflammation plays a key role in cartilage damage that occurs in osteoarthritis (OA). However, in vitro assessments of tissue-engineered constructs for cartilage regeneration generally do not consider their performance in the presence of inflammation. In this work, the chondrogenic differentiation potential of mesenchymal stromal cells (MSCs) was evaluated in the presence of both chondrogenic factors and inflammatory cytokines, and cartilage formation, degradative response, and inflammatory response were characterized. The addition of cytokines reduced cartilage production, increased cell proliferation, and resulted in an increase in inflammatory markers. Incorporation of hyaluronic acid (HA) had little impact on both collagen fibril microstructure and mechanical properties, two gel properties known to affect cell response, and thus allows the work to probe the biological impact of HA without the confounding effect of these gel properties. Regardless of in vitro environment, HA did not change cartilage production. The inflammatory response was similar with or without HA in terms of IL-6 and IL-10 secretion whereas IL-8 production exhibited some correlation with HA concentration as observed via a linear regression model. Additionally, in the presence of cytokines, inclusion of HA statistically decreased the gene- and protein-level expression of matrix metalloproteinase-13 (MMP-13). Thus, when exposed to both chondrogenic growth factors and inflammatory cytokines within a chondrogenic-promoting collagen I/II blended hydrogel, chondrogenic differentiation of MSCs was limited by the inflammatory environment. These findings emphasize the importance of understanding how biomaterials affect cell responses within disease-relevant inflammatory environments. © 2025 The Royal Society of Chemistry.

关键词： Fiber bonding

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Evaluation of hemiplegic gait using accelerometer

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Transactions of the Korean Institute of Electrical Engineers 2017年第11期66卷 1634-1640页

作者： Lee, Jun Seok Park, Sooji Shin, Hangsik Interdisciplinary Program of Biomedical Engineering Chonnam National University Gwangju Korea Republic of Department of Biomedical Engineering Chonnam National University Yeosu Korea Republic of

The study aims to distinguish hemiplegic gait and normal gait using simple wearable device and classification algorithm. Thus, we developed a wearable system equipped three axis accelerometer and three axis gyroscope. The developed wearable system was verified by clinical experiment. In experiment, twenty one normal subjects and twenty one patients undergoing stroke treatment were participated. Based on the measured inertial signal, a random forest algorithm was used to classify hemiplegic gait. Four-fold cross validation was applied to ensure the reliability of the results. To select optimal attributes, we applied the forward search algorithm with 10 times of repetition, then selected five most frequently attributes were chosen as a final attribute. The results of this study showed that 95.2% of accuracy in hemiplegic gait and normal gait classification and 77.4% of accuracy in hemiplegic-side and normal gait classification. © 2017 The Korean Institute of Electrical Engineers.

关键词： Patient treatment

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Wearable continuous diffusion-based skin gas analysis

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Nature Communications 2025年第1期16卷 1-15页

作者： Clausen, David Farley, Max Little, Abigail Kasper, Kevin Moreno, Joseph Limesand, Larissa Gutruf, Philipp Department of Biomedical Engineering University of Arizona Tucson 85721 AZ United States Department of Physiology University of Arizona Tucson 85721 AZ United States Department of Electrical and Computer Engineering University of Arizona Tucson 85721 AZ United States Bio5 Institute University of Arizona Tucson 85721 AZ United States Neuroscience Graduate Interdisciplinary Program University of Arizona Tucson 85721 AZ United States

Biophysical signals such as motion and optically acquired hemodynamics represent foundational sensing modalities for wearables. Expansion of this toolset is vital for the progression of digital medicine. Current efforts utilize biofluids such as sweat and interstitial fluid with primarily adhesively mounted sensors that are fundamentally limited by epidermal turnover. A class of potential biomarkers that is largely unexplored are gaseous emissions from the body. In this work, we introduce an approach to capture emission of gas from the skin with a leaky cavity designed to allow for diffusion-based ambient gas exchange with the environment. This approach, coupled with differential measurement of ambient and in-cavity gas concentrations, allows for the real-time analysis of sweat rate, VOCs, and CO₂ while performing everyday tasks. The resulting biosignals are recorded with temporal resolutions that exceed current methodology, providing unparalleled insight into physiological processes without requiring sensor replacement over weeks at a time. © The Author(s) 2025.

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Urine analysis in diluted situation using low-resolution Raman spectroscope

Urine analysis in diluted situation using low-resolution Ram...

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2005 27th Annual International Conference of the engineering in Medicine and Biology Society, IEEE-EMBS 2005

作者： Park, Cheol Soo Choi, Jong Min Park, Kwang Suk Interdisciplinary Program in Biomedical Engineering Seoul National University Department of Biomedical Engineering College of Medicine Seoul National University

ISBN: (纸本)0780387406

We could get valuable information about various diseases by analyzing urine of patients. For the diabetics, It has been very important to know the glucose concentration in their urine. Until now, there have been many methods to estimate the concentration but they were invasive and annoyed patients. The Low-Resolution Raman Spectroscopy (LRRS) could be an alternative method to be non-invasive and unconscious for patients who want to check the amount of their urine components. LRRS is not expensive and smaller than laboratory Raman spectroscope. And we want to attach it to the common toilet bowl. For the reason, we got the spectrum of diluted urine and predicted the glucose concentration. In addition, we tried to find very small amount of glucose. LRRS was adequate for measuring Raman signal of diluted urine and could find very small amount of glucose. This system will realize the observation of one's health condition every day without awareness. © 2005 IEEE.

关键词： Diagnosis

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High performance gamma-ray spectrometer based on Cs3Cu2I5 single crystal grown by room-temperature vacuum solvent-evaporation method

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Journal of Alloys and Compounds 2025年 1027卷

作者： Seo, Jiwon Song, Seungho Park, Minhwan Byun, Jangwon Park, Beomjun Park, Chansun Jang, Mee Yeom, Jung-Yeol Dept. of Health and Safety Convergence Science Korea University Seoul02841 Korea Republic of Interdisciplinary Program in Precision Public Health Korea University Seoul02841 Korea Republic of Dept. of Bioengineering Korea University Seoul02841 Korea Republic of Dept. of Materials Science and Engineering Korea University Seoul02841 Korea Republic of The Institute for High Technology Materials and Devices Korea University Seoul02841 Korea Republic of Global Health Technology Center Korea University Seoul02841 Korea Republic of Daejeon34057 Korea Republic of School of Biomedical Engineering Korea University Seoul02841 Korea Republic of

In this study, the properties of Cs3Cu2I5 (CCI) crystals grown using the Slow Vacuum Evaporation Technique (SVET) were examined. Crystals were grown at room temperature (300 K, 27 °C) under vacuum conditions, producing single crystals with maximum diameter of 13 mm over 23 days. We confirmed excellent crystallinity via X-ray diffraction (XRD), compositional uniformity via X-ray photoelectron spectroscopy (XPS), and homogeneity via electron probe micro analyzer (EPMA). UV-Vis measurements indicated a high transmittance of 83 % and a bandgap of 3.64 eV. The Stokes shift of 110 nm, smaller than previously reported values, contributed to faster decay times and improved low-energy detection feasibility. Time-resolved photoluminescence (TR-PL) showed a rapid decay component (4.1 ns), accounting for 95.11 % of the total decay, demonstrating superior properties compared to existing reports. The gamma-ray detection capabilities of the CCI crystals were evaluated using six radioactive sources (Am-241, Ba-133, Co-57, Na-22, Cs-137, and Mn-54), achieving excellent energy resolution, including 5.2 % at 662 keV. The crystals displayed a highly linear response to gamma radiation (R² = 0.99998) with a light yield of 55,613 photons/MeV. Moreover, assessments of multiple crystals grown under identical conditions showed consistent performance with a coefficient of variation (CV) of 1.23 %. These findings confirm that SVET is a highly effective and cost-efficient method for producing high-quality CCI crystals, offering significant advantages over other growth techniques. © 2025 Elsevier B.V.

关键词： Gamma ray spectrometers

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Design of an Fc Mutation to Abrogate Fcγ Receptor Binding Based on Residue Interaction Network Analysis

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ACS Synthetic Biology 2025年第5期14卷 2025 Apr 29页

作者： Jebamani, Petrina Jo, Migyeong Park, Suhyun Kim, Suyeon Jung, Sang Taek Lee, Sun-Gu Wu, Sangwook Department of Chemical Engineering Pusan National University Busan 46241 South Korea Institute of Chemical Processes Seoul National University Seoul 08826 South Korea Department of Chemical and Biological Engineering Seoul National University Seoul 08826 South Korea Department of Physics Pukyong National University Busan 48513 South Korea Interdisciplinary Program for Bioengineering Seoul National University Seoul 08826 South Korea PharmCADD 1102-ho 60 Centum Jungang-ro Haeundae-gu Busan 48059 South Korea Department of Biomedical Sciences Graduate School Korea University Seongbuk-gu Seoul 02841 South Korea BK21 Graduate Program Department of Biomedical Sciences Korea University College of Medicine Seoul 02841 South Korea

Immunoglobulins mediate their immune responses through interactions with Fc γ-receptors (FcγRs) on immune cells, triggering crucial responses such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). While enhancing these interactions can be beneficial, in certain therapeutic scenarios, such as cytokine or receptor blockade therapies, it is critical to reduce FcγR binding to avoid adverse immune reactions. This study aims to design negative mutations in the Fc region to reduce Fcγ receptor binding based on the residue interaction network analysis. The mutation sites of Fc were targeted through betweenness centrality analysis, and mutations were designed by focusing on hydrophobic to hydrophilic residue changes. The negative effect of the designed mutants on binding affinity was verified by previous reports and binding experiments. From this study, we identified a new Fc variant candidate (V263(B)D) that lacks a binding affinity for Fcγ receptors. This research highlights a strategic approach for designing Fc mutations that effectively reduce immune activation, which may be valuable in therapeutic contexts, where immune response moderation is crucial. © 2025 American Chemical Society.

关键词： betweenness centrality Fc FcγRIIIa IgG inhibiting mutations residue interaction network analysis

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biomedical data and AI

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Science China Life Sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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