首页 > 最新文献

bioRxiv - Biophysics最新文献

英文 中文
Mechanical Profiling of Biopolymer Condensates through Acoustic Trapping 通过声学捕获对生物聚合物凝结物进行机械剖面分析
Pub Date : 2024-09-19 DOI: 10.1101/2024.09.16.613217
Kichitaro Nakajima, Tomas Sneideris, Lydia L. Good, Nadia Aicha Erkamp, Hirotsugu Ogi, Tuomas Knowles
Characterizing the mechanical properties of single colloids is a central problem in soft matter physics. It also plays a key role in cell biology through biopolymer condensates, which function as membraneless compartments. Such systems can also malfunction, leading to the onset of a number of diseases, including many neurodegenerative diseases; the functional and pathological condensates are commonly differentiated by their mechanical signature. Probing the mechanical properties of biopolymer condensates at the single particle level has, however, remained challenging. In this study, we demonstrate that acoustic trapping can be used to profile the mechanical properties of single condensates in a contactless manner. We find that acoustic fields exert the acoustic radiation force on condensates, leading to their migration to a trapping point where acoustic potential energy is minimized. Furthermore, our results show that the Brownian motion fluctuation of condensates in an acoustic potential well is an accurate probe for their bulk modulus. We demonstrate that this framework can detect the change in the bulk modulus of polyadenylic acid condensates in response to changes in environmental conditions. Our results show that acoustic trapping opens up a novel path to profile the mechanical properties of soft colloids at the single particle level in a non-invasive manner with applications in biology, materials science, and beyond.
表征单个胶体的机械特性是软物质物理学的一个核心问题。它还通过生物聚合物凝聚体在细胞生物学中发挥关键作用,生物聚合物凝聚体具有无膜隔室的功能。这种系统也可能发生故障,导致多种疾病的发生,包括许多神经退行性疾病;功能性凝聚体和病理凝聚体通常通过其机械特征来区分。然而,在单颗粒水平探测生物聚合物凝聚体的机械特性仍然具有挑战性。在这项研究中,我们证明了声学捕集可用于以非接触方式剖析单个凝聚体的机械特性。我们发现,声场会对凝聚体施加声辐射力,导致它们迁移到声势能最小的捕集点。此外,我们的研究结果表明,冷凝物在声势阱中的布朗运动波动是对其体积模量的精确探测。我们证明了这一框架可以检测多腺苷酸凝聚体的体积模量随环境条件变化而发生的变化。我们的研究结果表明,声学捕集开辟了一条新的途径,可以在单颗粒水平上以非侵入的方式剖析软胶体的机械特性,并将其应用于生物学、材料科学等领域。
{"title":"Mechanical Profiling of Biopolymer Condensates through Acoustic Trapping","authors":"Kichitaro Nakajima, Tomas Sneideris, Lydia L. Good, Nadia Aicha Erkamp, Hirotsugu Ogi, Tuomas Knowles","doi":"10.1101/2024.09.16.613217","DOIUrl":"https://doi.org/10.1101/2024.09.16.613217","url":null,"abstract":"Characterizing the mechanical properties of single colloids is a central problem in soft matter physics. It also plays a key role in cell biology through biopolymer condensates, which function as membraneless compartments. Such systems can also malfunction, leading to the onset of a number of diseases, including many neurodegenerative diseases; the functional and pathological condensates are commonly differentiated by their mechanical signature. Probing the mechanical properties of biopolymer condensates at the single particle level has, however, remained challenging. In this study, we demonstrate that acoustic trapping can be used to profile the mechanical properties of single condensates in a contactless manner. We find that acoustic fields exert the acoustic radiation force on condensates, leading to their migration to a trapping point where acoustic potential energy is minimized. Furthermore, our results show that the Brownian motion fluctuation of condensates in an acoustic potential well is an accurate probe for their bulk modulus. We demonstrate that this framework can detect the change in the bulk modulus of polyadenylic acid condensates in response to changes in environmental conditions. Our results show that acoustic trapping opens up a novel path to profile the mechanical properties of soft colloids at the single particle level in a non-invasive manner with applications in biology, materials science, and beyond.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
De-novo design of actively spinning and gyrating spherical micro-vesicles 主动旋转和回旋球形微囊的全新设计
Pub Date : 2024-09-19 DOI: 10.1101/2024.09.17.613442
Veerpal Kaur, Subhashree S. Khuntia, Charu Taneja, Abhishek Chaudhuri, K. P. Yogendran, Sabyasachi Rakshit
Engineering spherical self-propelled swimmers that exhibit rotation and directed translation has posed a significant experimental challenge in biomedicine design. Often a secondary external field or asymmetric geometry is employed to generate rotation, complicating the design process. In this work, we utilize spherical Giant Unilamellar Vesicles (GUVs) as chassis and enzymes undergoing cyclic, non-reciprocal conformational changes as power units to establish design principles to synthesize autonomous spherical micro-rotors. Leveraging transient interactions, we induce spontaneous symmetry-breaking in enzyme distribution on GUVs, enabling diverse movements from pure spinning to spiral 3D trajectories. With this design, we now open new avenues for advancing self-propelled systems with biocompatible materials, unlocking innovations in biomedical applications.
在生物医学设计中,设计出具有旋转和定向平移功能的球形自推进游泳器是一项重大的实验挑战。通常情况下,需要使用二级外部磁场或不对称几何形状来产生旋转,从而使设计过程变得更加复杂。在这项工作中,我们利用球形巨型单拉美拉尔囊泡 (GUV) 作为底盘,并利用发生周期性、非互惠构象变化的酶作为动力单元,建立了合成自主球形微型转子的设计原则。利用瞬时相互作用,我们诱发了酶在 GUVs 上分布的自发对称性破坏,从而实现了从纯粹旋转到螺旋三维轨迹的多种运动。有了这种设计,我们现在可以利用生物兼容材料为推进自推进系统开辟新的途径,从而开启生物医学应用领域的创新。
{"title":"De-novo design of actively spinning and gyrating spherical micro-vesicles","authors":"Veerpal Kaur, Subhashree S. Khuntia, Charu Taneja, Abhishek Chaudhuri, K. P. Yogendran, Sabyasachi Rakshit","doi":"10.1101/2024.09.17.613442","DOIUrl":"https://doi.org/10.1101/2024.09.17.613442","url":null,"abstract":"Engineering spherical self-propelled swimmers that exhibit rotation and directed translation has posed a significant experimental challenge in biomedicine design. Often a secondary external field or asymmetric geometry is employed to generate rotation, complicating the design process. In this work, we utilize spherical Giant Unilamellar Vesicles (GUVs) as chassis and enzymes undergoing cyclic, non-reciprocal conformational changes as power units to establish design principles to synthesize autonomous spherical micro-rotors. Leveraging transient interactions, we induce spontaneous symmetry-breaking in enzyme distribution on GUVs, enabling diverse movements from pure spinning to spiral 3D trajectories. With this design, we now open new avenues for advancing self-propelled systems with biocompatible materials, unlocking innovations in biomedical applications.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Localization of Albumin with Correlative Super Resolution Light- and Electron Microscopy in the Kidney 用相关超分辨光镜和电子显微镜确定肾脏中白蛋白的位置
Pub Date : 2024-09-19 DOI: 10.1101/2024.09.16.613238
Alexandra N. Birtasu, Utz H. Ermel, Johanna V. Rahm, Anja Seybert, Benjamin Flottmann, Mike Heilemann, Florian Grahammer, Achilleas S Frangakis
The functioning of vertebrate life relies on renal filtration of surplus fluid and elimination of low-molecular-weight waste products, while keeping serum proteins in the blood. In disease, however, there is leak of serum proteins and tracing them to identify the leaking position within tissue with a nanometer resolution poses a significant challenge. Correlative microscopy integrates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Using chemical tagging of albumin with synthetic fluorophores we achieve protein-specific labeling that preserve their post-embedding fluorescence after high-pressure freezing and freeze-substitution of murine kidney tissue. Using advanced registration techniques for super-resolution correlative light and electron microscopy, we can localize the labeled albumin with a high precision in the x-y plane of electron micrographs and cartograph its distribution. Thereby we can quantify the albumin concentration and measure a linear reduction gradient across the kidney filtration barrier. Our study shows the feasibility of combining different microscopy contrasts for tracing fluorescently labeled protein markers with super resolution in various tissue samples and opens new perspectives for correlative imaging in volume electron microscopy.
脊椎动物的生命机能依赖于肾脏过滤多余液体和排出低分子量废物,同时保持血液中的血清蛋白。然而,在疾病情况下,血清蛋白会发生泄漏,要以纳米分辨率追踪血清蛋白以确定其在组织内的泄漏位置,是一项重大挑战。相关显微镜将荧光蛋白标记的特异性与高分辨率电子显微图像相结合。利用合成荧光团对白蛋白进行化学标记,我们实现了蛋白质特异性标记,在对小鼠肾脏组织进行高压冷冻和冷冻置换后仍能保持其包埋后的荧光。利用先进的超分辨率相关光镜和电子显微镜配准技术,我们可以在电子显微图像的 x-y 平面上高精度地定位标记的白蛋白,并绘制其分布图。因此,我们可以量化白蛋白浓度,并测量肾脏滤过屏障上的线性减少梯度。我们的研究表明,结合不同的显微对比度,在各种组织样本中以超分辨率追踪荧光标记的蛋白质标记物是可行的,并为体视电子显微镜中的相关成像开辟了新的前景。
{"title":"Localization of Albumin with Correlative Super Resolution Light- and Electron Microscopy in the Kidney","authors":"Alexandra N. Birtasu, Utz H. Ermel, Johanna V. Rahm, Anja Seybert, Benjamin Flottmann, Mike Heilemann, Florian Grahammer, Achilleas S Frangakis","doi":"10.1101/2024.09.16.613238","DOIUrl":"https://doi.org/10.1101/2024.09.16.613238","url":null,"abstract":"The functioning of vertebrate life relies on renal filtration of surplus fluid and elimination of low-molecular-weight waste products, while keeping serum proteins in the blood. In disease, however, there is leak of serum proteins and tracing them to identify the leaking position within tissue with a nanometer resolution poses a significant challenge. Correlative microscopy integrates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Using chemical tagging of albumin with synthetic fluorophores we achieve protein-specific labeling that preserve their post-embedding fluorescence after high-pressure freezing and freeze-substitution of murine kidney tissue. Using advanced registration techniques for super-resolution correlative light and electron microscopy, we can localize the labeled albumin with a high precision in the x-y plane of electron micrographs and cartograph its distribution. Thereby we can quantify the albumin concentration and measure a linear reduction gradient across the kidney filtration barrier. Our study shows the feasibility of combining different microscopy contrasts for tracing fluorescently labeled protein markers with super resolution in various tissue samples and opens new perspectives for correlative imaging in volume electron microscopy.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell-derived matrices mechanics as a functional read-out in Collagen VI-related Congenital Muscular Dystrophies 细胞衍生基质力学作为胶原蛋白 VI 相关先天性肌肉萎缩症的功能读数
Pub Date : 2024-09-18 DOI: 10.1101/2024.09.13.612824
Tom White, Aristides Lopez-Marquez, Carmen Badosa, Cecilia Jimenez-Mallebrera, Josep Samitier, Marina I Giannotti, Anna Lagunas
Collagen VI-related congenital muscular dystrophies (COL6-RDs) are a set of neuromuscular conditions caused by pathogenic variants found in any of the three COL6 genes. The phenotypic expression of the disease does not directly correlate with the genetic background producing an overlapping spectrum of clinical phenotypes that goes from the mild Bethlem myopathy (BM) to the severe Ulrich congenital muscular dystrophy (UCMD). Diagnosis includes genetic confirmation of the disease and categorization of the phenotype based on maximum motor ability. The development of new tools able to identify phenotype traits can significantly contribute to the diagnosis and prognosis of COL6-RDs. Mutations occurring in COL6 genes result in deficiency or dysfunction of COL6 incorporated into the extracellular matrix (ECM) of connective tissues, affecting its fibrillar structure. Our research group has established personalized pre-clinical models of COL6-RDs based on cell-derived matrices (CDMs), which allowed the direct observation of the fibrillar organization of the ECM in samples derived from patients, and to compare features amongst different phenotypes. Here, we have characterized the mechanical properties of CDMs from patients using atomic force microscopy-based force spectroscopy (AFM-FS). We observed that the elastic modulus (E) varies with the phenotype, and that it correlates with COL6 organization in the CDMs. We additionally used AFM-FS to evaluate matrices derived from genetically edited cells, which resulted in E value restoration compared to control samples. Altogether, these results anticipate the potential of mechanical analysis of CDMs as a complementary clinical tool, providing phenotypic information about COL6-RDs and their response to gene therapies.
胶原蛋白 VI 相关先天性肌营养不良症(COL6-RDs)是由三个 COL6 基因中任何一个基因的致病变体引起的一系列神经肌肉疾病。该病的表型表现与遗传背景并不直接相关,临床表型重叠,从轻微的伯利姆肌病(BM)到严重的乌尔里希先天性肌营养不良症(UCMD)。诊断包括疾病的基因确认和基于最大运动能力的表型分类。开发能够识别表型特征的新工具可极大地促进 COL6-RD 的诊断和预后。COL6 基因突变会导致结缔组织细胞外基质(ECM)中的 COL6 缺乏或功能障碍,影响其纤维结构。我们的研究小组基于细胞衍生基质(CDMs)建立了个性化的 COL6-RD 临床前模型,可直接观察患者样本中 ECM 的纤维组织,并比较不同表型的特征。在此,我们使用基于原子力显微镜的力谱仪(AFM-FS)鉴定了患者 CDMs 的机械特性。我们观察到弹性模量(E)随表型而变化,并且与 CDMs 中的 COL6 组织相关。此外,我们还使用 AFM-FS 评估了来自基因编辑细胞的基质,结果发现与对照样本相比,E 值有所恢复。总之,这些结果预示着 CDMs 的机械分析有望成为一种补充性临床工具,提供有关 COL6-RD 及其对基因疗法反应的表型信息。
{"title":"Cell-derived matrices mechanics as a functional read-out in Collagen VI-related Congenital Muscular Dystrophies","authors":"Tom White, Aristides Lopez-Marquez, Carmen Badosa, Cecilia Jimenez-Mallebrera, Josep Samitier, Marina I Giannotti, Anna Lagunas","doi":"10.1101/2024.09.13.612824","DOIUrl":"https://doi.org/10.1101/2024.09.13.612824","url":null,"abstract":"Collagen VI-related congenital muscular dystrophies (COL6-RDs) are a set of neuromuscular conditions caused by pathogenic variants found in any of the three COL6 genes. The phenotypic expression of the disease does not directly correlate with the genetic background producing an overlapping spectrum of clinical phenotypes that goes from the mild Bethlem myopathy (BM) to the severe Ulrich congenital muscular dystrophy (UCMD). Diagnosis includes genetic confirmation of the disease and categorization of the phenotype based on maximum motor ability. The development of new tools able to identify phenotype traits can significantly contribute to the diagnosis and prognosis of COL6-RDs. Mutations occurring in COL6 genes result in deficiency or dysfunction of COL6 incorporated into the extracellular matrix (ECM) of connective tissues, affecting its fibrillar structure. Our research group has established personalized pre-clinical models of COL6-RDs based on cell-derived matrices (CDMs), which allowed the direct observation of the fibrillar organization of the ECM in samples derived from patients, and to compare features amongst different phenotypes. Here, we have characterized the mechanical properties of CDMs from patients using atomic force microscopy-based force spectroscopy (AFM-FS). We observed that the elastic modulus (E) varies with the phenotype, and that it correlates with COL6 organization in the CDMs. We additionally used AFM-FS to evaluate matrices derived from genetically edited cells, which resulted in E value restoration compared to control samples. Altogether, these results anticipate the potential of mechanical analysis of CDMs as a complementary clinical tool, providing phenotypic information about COL6-RDs and their response to gene therapies.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A combined approach to extract rotational dynamics of globular proteins undergoing liquid-liquid phase separation 提取发生液-液相分离的球状蛋白质旋转动力学的组合方法
Pub Date : 2024-09-18 DOI: 10.1101/2024.09.17.613388
Dominik Gendreizig, Abhishek Kalarikkal, Simon L. Holtbrügge, Saumyak Mukherjee, Laura Galazzo, Svetlana Kucher, Arnulf Rosspeintner, Lars V. Schäfer, Enrica Bordignon
The formation of protein condensates (droplets) via liquid-liquid phase separation (LLPS) is a commonly observed phenomenon in vitro. Changing the environmental properties with cosolutes, molecular crowders, protein partners, temperature, pressure, etc. was shown to favour or disfavour the formation of protein droplets by fine-tuning the water-water, water-protein and protein-protein interactions. Therefore, these environmental properties and their spatiotemporal fine-tuning are likely to be important also in a cellular context at the existing protein expression levels. One of the key physicochemical properties of biomolecules impacted by molecular crowding is diffusion, which determines the viscoelastic behaviour of the condensates. Here we investigate the change in the rotational diffusion of γD-crystallin, undergoing LLPS in vitro in aqueous solutions in absence and presence of cosolutes. We studied its rotational dynamics using molecular dynamics simulations (MD), electron paramagnetic resonance (EPR) spectroscopy and fluorescence spectroscopy. MD simulations performed under dilute and crowded conditions show that the rotational diffusion of crystallin in water is retarded by one to two orders of magnitude in the condensed phase. To obtain the rotational dynamics in the dilute phase we used fluorescence anisotropy and to extract the retardation factor in in the condensed phase we used spin-labeled γD-crystallin proteins as EPR viscosity nanoprobes. Aided by a viscosity nanoruler calibrated with solutions at increasing sucrose concentrations, we validate the rotational diffusion retardation predicted by MD simulations. This study underlines the predictive power of MD simulations and showcases the use of a sensitive EPR nanoprobe to extract the viscosity of biomolecular condensates.
通过液-液相分离(LLPS)形成蛋白质凝聚物(液滴)是体外观察到的常见现象。通过微调水-水、水-蛋白质和蛋白质-蛋白质之间的相互作用,改变共溶质、分子排阻剂、蛋白质伙伴、温度、压力等环境属性,有利于或不利于蛋白质液滴的形成。因此,这些环境特性及其时空微调很可能在现有蛋白质表达水平的细胞环境中也很重要。扩散是受分子拥挤影响的生物大分子的关键物理化学特性之一,它决定了凝聚物的粘弹性行为。在此,我们研究了γ-D-结晶素在体外水溶液中,在没有共溶质和有共溶质的情况下进行 LLPS 时旋转扩散的变化。我们利用分子动力学模拟(MD)、电子顺磁共振(EPR)光谱和荧光光谱对其旋转动力学进行了研究。在稀释和拥挤条件下进行的 MD 模拟显示,结晶素在水中的旋转扩散在凝聚相中会被延缓一到两个数量级。为了获得稀释相中的旋转动力学,我们使用了荧光各向异性;为了提取凝聚相中的延迟因子,我们使用了自旋标记的γD-结晶蛋白作为 EPR 粘度纳米探针。在用蔗糖浓度不断增加的溶液校准的粘度纳米标尺的帮助下,我们验证了 MD 模拟预测的旋转扩散延迟。这项研究强调了 MD 模拟的预测能力,并展示了使用灵敏的 EPR 纳米探针提取生物分子凝聚物粘度的方法。
{"title":"A combined approach to extract rotational dynamics of globular proteins undergoing liquid-liquid phase separation","authors":"Dominik Gendreizig, Abhishek Kalarikkal, Simon L. Holtbrügge, Saumyak Mukherjee, Laura Galazzo, Svetlana Kucher, Arnulf Rosspeintner, Lars V. Schäfer, Enrica Bordignon","doi":"10.1101/2024.09.17.613388","DOIUrl":"https://doi.org/10.1101/2024.09.17.613388","url":null,"abstract":"The formation of protein condensates (droplets) via liquid-liquid phase separation (LLPS) is a commonly observed phenomenon in vitro. Changing the environmental properties with cosolutes, molecular crowders, protein partners, temperature, pressure, etc. was shown to favour or disfavour the formation of protein droplets by fine-tuning the water-water, water-protein and protein-protein interactions. Therefore, these environmental properties and their spatiotemporal fine-tuning are likely to be important also in a cellular context at the existing protein expression levels. One of the key physicochemical properties of biomolecules impacted by molecular crowding is diffusion, which determines the viscoelastic behaviour of the condensates. Here we investigate the change in the rotational diffusion of γD-crystallin, undergoing LLPS in vitro in aqueous solutions in absence and presence of cosolutes. We studied its rotational dynamics using molecular dynamics simulations (MD), electron paramagnetic resonance (EPR) spectroscopy and fluorescence spectroscopy. MD simulations performed under dilute and crowded conditions show that the rotational diffusion of crystallin in water is retarded by one to two orders of magnitude in the condensed phase. To obtain the rotational dynamics in the dilute phase we used fluorescence anisotropy and to extract the retardation factor in in the condensed phase we used spin-labeled γD-crystallin proteins as EPR viscosity nanoprobes. Aided by a viscosity nanoruler calibrated with solutions at increasing sucrose concentrations, we validate the rotational diffusion retardation predicted by MD simulations. This study underlines the predictive power of MD simulations and showcases the use of a sensitive EPR nanoprobe to extract the viscosity of biomolecular condensates.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unlocking precision: How corneal cell area analysis revolutionises post-transplant stem cell monitoring 实现精准:角膜细胞面积分析如何彻底改变移植后干细胞监测
Pub Date : 2024-09-18 DOI: 10.1101/2024.09.17.612429
Patrick Parkinson, Irina Makarenko, Oliver J Baylis, Gustavo S Figueiredo, Majlinda Lako, Anvar Shukurov, Francisco C Figueiredo, Laura E Wadkin
The corneal epithelium is maintained by limbal stem cells (LSCs). Dysfunction of the LSCs, resulting from chemical and thermal burns, contact lens-related disease, congenial disorders, among other conditions, leads to limbal stem cell deficiency (LSCD), a sight-threatening condition. An effective treatment of LSCD, with 76% of patients reporting regained sight up to 24 months after the operation, consists of transplanting ex-vivo cultured LSCs from the patient's other healthy eye (i.e. autologous) or donor (i.e. allogeneic) to the affected eye. The post-operative assessment of corneal recovery is crucial but relies on ponderous and generally subjective visual inspection of a large number of microscopic images of the corneal epithelial cells, relying on the personal experience of the practitioner to interpret imprecise, qualitative diagnostic criteria. From a unique library of 100,000 cornea cell images from 34 patients, we have randomly selected 10 individuals (3,668 images) to demonstrate that the frequency distribution of the epithelial cell areas is a sensitive diagnostic tool of the corneal epithelium status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the frequency distribution becomes narrower with high statistical confidence and eventually approaches that of the healthy cornea. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells have a hexagonal shape. We also show that the corneal epithelial cell area distribution and its variation with the depth within the cornea are specific to each patient.
角膜上皮由角膜缘干细胞(LSCs)维持。由于化学和热烧伤、接触镜相关疾病、先天性疾病等原因导致的角膜缘干细胞功能障碍,会导致角膜缘干细胞缺乏症(LSCD),这是一种威胁视力的疾病。角膜缘干细胞缺乏症的有效治疗方法是将患者另一只健康眼睛(即自体)或捐献者(即异体)体内培养的角膜缘干细胞移植到患眼,76%的患者在术后24个月内恢复了视力。角膜恢复的术后评估至关重要,但这依赖于对大量角膜上皮细胞显微图像进行深思熟虑的、通常是主观的目视检查,并依靠医生的个人经验来解释不精确的定性诊断标准。我们从一个包含 34 名患者 100,000 张角膜细胞图像的独特图书馆中随机抽取了 10 人(3,668 张图像),证明上皮细胞区域的频率分布是角膜上皮状态的灵敏诊断工具。手术成功后,细胞区域的分布相当平缓,反映出细胞区域范围异常广泛。随着角膜的恢复,频率分布变窄,统计置信度变高,最终接近健康角膜的频率分布。尽管人们普遍认为健康的角膜上皮细胞呈六角形,但角膜上皮细胞的形状与角膜状态无关。我们还发现,角膜上皮细胞的面积分布及其随角膜深度的变化是每个患者所特有的。
{"title":"Unlocking precision: How corneal cell area analysis revolutionises post-transplant stem cell monitoring","authors":"Patrick Parkinson, Irina Makarenko, Oliver J Baylis, Gustavo S Figueiredo, Majlinda Lako, Anvar Shukurov, Francisco C Figueiredo, Laura E Wadkin","doi":"10.1101/2024.09.17.612429","DOIUrl":"https://doi.org/10.1101/2024.09.17.612429","url":null,"abstract":"The corneal epithelium is maintained by limbal stem cells (LSCs). Dysfunction of the LSCs, resulting from chemical and thermal burns, contact lens-related disease, congenial disorders, among other conditions, leads to limbal stem cell deficiency (LSCD), a sight-threatening condition. An effective treatment of LSCD, with 76% of patients reporting regained sight up to 24 months after the operation, consists of transplanting ex-vivo cultured LSCs from the patient's other healthy eye (i.e. autologous) or donor (i.e. allogeneic) to the affected eye. The post-operative assessment of corneal recovery is crucial but relies on ponderous and generally subjective visual inspection of a large number of microscopic images of the corneal epithelial cells, relying on the personal experience of the practitioner to interpret imprecise, qualitative diagnostic criteria. From a unique library of 100,000 cornea cell images from 34 patients, we have randomly selected 10 individuals (3,668 images) to demonstrate that the frequency distribution of the epithelial cell areas is a sensitive diagnostic tool of the corneal epithelium status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the frequency distribution becomes narrower with high statistical confidence and eventually approaches that of the healthy cornea. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells have a hexagonal shape. We also show that the corneal epithelial cell area distribution and its variation with the depth within the cornea are specific to each patient.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Monomers to Oligomers: Structural Mechanism of Receptor-Triggered MyD88 Assembly in Innate Immune Signaling 从单体到寡聚体:先天性免疫信号中受体触发 MyD88 组装的结构机制
Pub Date : 2024-09-18 DOI: 10.1101/2024.09.13.612588
Kazuki Kasai, Kayo Imamura, Masatoshi Uno, Naotaka Sekiyama, Tomoko Miyata, Fumiaki Makino, Ryusei Yamada, Yoshiki Takahashi, Noriyuki Kodera, Keiichi Namba, Hidenori Ohnishi, Akihiro Narita, Hiroki Konno, Hidehito Tochio
MyD88 plays a pivotal role in Toll-like receptor (TLR) and interleukin-1 family signaling through its oligomerization upon receptor activation, leading to downstream protein recruitment. The Toll/interleukin-1 receptor domain of MyD88 (TIRMyD88) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. We investigated the structure of TIRMyD88 oligomers and their interactions with TLRs. Cryoelectron microscopy revealed that tandemly arrayed TIRMyD88 subunits formed an antiparallel double-stranded filament that could further form rings and cylindrical filaments. Moreover, the self-assembly of TIRMyD88 in vitro was markedly accelerated by dimeric rather than monomeric receptor TIRs, possibly reflecting the signal initiation step in vivo. High-speed atomic force microscopy further captured the dynamic processes of oligomerization of TIRMyD88, in addition to its direct interaction with the receptor TIRs. Based on these results, a novel regulatory mechanism of TIRMyD88 oligomerization underlying the signal initiation step was revealed.
MyD88在Toll样受体(TLR)和白细胞介素-1家族信号传导过程中发挥着关键作用,它在受体激活时会寡聚,从而导致下游蛋白的招募。MyD88的Toll/白细胞介素-1受体结构域(TIRMyD88)负责这种受体介导的寡聚化,但其中涉及的详细机制仍不清楚。我们研究了 TIRMyD88 寡聚体的结构及其与 TLR 的相互作用。冷冻电镜显示,串联排列的 TIRMyD88 亚基形成了反平行双链丝,并可进一步形成环状和圆柱状丝。此外,体外 TIRMyD88 的自组装在二聚体而非单体受体 TIR 的作用下明显加快,这可能反映了体内的信号启动步骤。高速原子力显微镜进一步捕捉到了 TIRMyD88 除了与受体 TIRs 直接相互作用外,还发生了寡聚化的动态过程。基于这些结果,揭示了信号起始步骤所依赖的 TIRMyD88 寡聚化的新型调控机制。
{"title":"From Monomers to Oligomers: Structural Mechanism of Receptor-Triggered MyD88 Assembly in Innate Immune Signaling","authors":"Kazuki Kasai, Kayo Imamura, Masatoshi Uno, Naotaka Sekiyama, Tomoko Miyata, Fumiaki Makino, Ryusei Yamada, Yoshiki Takahashi, Noriyuki Kodera, Keiichi Namba, Hidenori Ohnishi, Akihiro Narita, Hiroki Konno, Hidehito Tochio","doi":"10.1101/2024.09.13.612588","DOIUrl":"https://doi.org/10.1101/2024.09.13.612588","url":null,"abstract":"MyD88 plays a pivotal role in Toll-like receptor (TLR) and interleukin-1 family signaling through its oligomerization upon receptor activation, leading to downstream protein recruitment. The Toll/interleukin-1 receptor domain of MyD88 (TIRMyD88) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. We investigated the structure of TIRMyD88 oligomers and their interactions with TLRs. Cryoelectron microscopy revealed that tandemly arrayed TIRMyD88 subunits formed an antiparallel double-stranded filament that could further form rings and cylindrical filaments. Moreover, the self-assembly of TIRMyD88 in vitro was markedly accelerated by dimeric rather than monomeric receptor TIRs, possibly reflecting the signal initiation step in vivo. High-speed atomic force microscopy further captured the dynamic processes of oligomerization of TIRMyD88, in addition to its direct interaction with the receptor TIRs. Based on these results, a novel regulatory mechanism of TIRMyD88 oligomerization underlying the signal initiation step was revealed.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamics of microcompartment formation at the mitosis-to-G1 transition 有丝分裂向 G1 转变过程中微室形成的动态变化
Pub Date : 2024-09-16 DOI: 10.1101/2024.09.16.611917
Viraat Y Goel, Nicholas G Aboreden, James M Jusuf, Haoyue Zhang, Luisa Mori, Leonid A Mirny, Gerd Blobel, Edward J Banigan, Anders Sejr Hansen
As cells exit mitosis and enter G1, mitotic chromosomes decompact and transcription is reestablished. Previously, Hi-C studies showed that essentially all interphase 3D genome features including A/B-compartments, TADs, and CTCF loops, are lost during mitosis. However, Hi-C remains insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements (CREs). We therefore applied Region Capture Micro-C to cells from mitosis to G1. Unexpectedly, we observe microcompartments in prometaphase, which further strengthen in ana/telophase before gradually weakening in G1. Loss of loop extrusion through condensin depletion differentially impacts microcompartments and large A/B-compartments, suggesting that they are partially distinct. Using polymer modeling, we show that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion activity, explaining why ana/telophase likely provides a particularly favorable environment. Our results suggest that CREs exhibit intrinsic homotypic affinity leading to microcompartment formation, which may explain transient transcriptional spiking observed upon mitotic exit.
当细胞退出有丝分裂进入 G1 期时,有丝分裂染色体会解聚,转录也会重新建立。之前的 Hi-C 研究表明,在有丝分裂过程中,基本上所有间期三维基因组特征都会消失,包括 A/B 小室、TAD 和 CTCF 环。然而,Hi-C 对微空腔、嵌套的顺式调控元件(CRE)之间的焦点相互作用等特征仍然不敏感。因此,我们对有丝分裂至 G1 期的细胞进行了区域捕获 Micro-C。出乎意料的是,我们在有丝分裂期观察到了微小空隙,这种空隙在有丝分裂期/分裂期进一步加强,然后在 G1 期逐渐减弱。冷凝素耗竭导致的环路挤压损失对微空腔和大 A/B 空腔产生了不同的影响,这表明它们有部分区别。通过聚合物建模,我们发现染色质压实有利于微隔室的形成,而环路挤压活动则不利于微隔室的形成,这就解释了为什么ana/telophase可能提供了一个特别有利的环境。我们的研究结果表明,CREs 表现出内在的同型亲和力,从而导致微室的形成,这或许可以解释有丝分裂结束时观察到的瞬时转录尖峰现象。
{"title":"Dynamics of microcompartment formation at the mitosis-to-G1 transition","authors":"Viraat Y Goel, Nicholas G Aboreden, James M Jusuf, Haoyue Zhang, Luisa Mori, Leonid A Mirny, Gerd Blobel, Edward J Banigan, Anders Sejr Hansen","doi":"10.1101/2024.09.16.611917","DOIUrl":"https://doi.org/10.1101/2024.09.16.611917","url":null,"abstract":"As cells exit mitosis and enter G1, mitotic chromosomes decompact and transcription is reestablished. Previously, Hi-C studies showed that essentially all interphase 3D genome features including A/B-compartments, TADs, and CTCF loops, are lost during mitosis. However, Hi-C remains insensitive to features such as microcompartments, nested focal interactions between cis-regulatory elements (CREs). We therefore applied Region Capture Micro-C to cells from mitosis to G1. Unexpectedly, we observe microcompartments in prometaphase, which further strengthen in ana/telophase before gradually weakening in G1. Loss of loop extrusion through condensin depletion differentially impacts microcompartments and large A/B-compartments, suggesting that they are partially distinct. Using polymer modeling, we show that microcompartment formation is favored by chromatin compaction and disfavored by loop extrusion activity, explaining why ana/telophase likely provides a particularly favorable environment. Our results suggest that CREs exhibit intrinsic homotypic affinity leading to microcompartment formation, which may explain transient transcriptional spiking observed upon mitotic exit.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure of small HBV surface antigen reveals mechanism of dimer formation 小型 HBV 表面抗原的结构揭示了二聚体的形成机制
Pub Date : 2024-09-15 DOI: 10.1101/2024.09.13.612767
Xiao He, Yunlu Kang, Weiyu Tao, Jiaxuan Xu, Xiaoyu Liu, Lei Chen
Hepatitis B surface antigen (HBsAg), the only membrane protein on the HBV viral envelope, plays essential roles in HBV assembly, viral release, host cell attachment, and entry. It is also the target of neutralizing antibodies. Despite its functional and therapeutic importance, the detailed structure of HBsAg has remained enigmatic. Here, we present the core structure of HBsAg at 3.6 A resolution, determined using recombinant small spherical subviral particles (SVPs). The structure reveals how two HBsAg monomers interact to form a dimer, which is the basic building block of SVPs.
乙型肝炎表面抗原(HBsAg)是乙型肝炎病毒包膜上唯一的膜蛋白,在乙型肝炎病毒组装、病毒释放、宿主细胞附着和进入过程中发挥着重要作用。它也是中和抗体的靶标。尽管 HBsAg 具有重要的功能和治疗作用,但它的详细结构一直是个谜。在这里,我们利用重组小球形亚病毒颗粒(SVPs)测定了 3.6 A 分辨率的 HBsAg 核心结构。该结构揭示了两个 HBsAg 单体如何相互作用形成二聚体,而二聚体正是 SVP 的基本组成单元。
{"title":"Structure of small HBV surface antigen reveals mechanism of dimer formation","authors":"Xiao He, Yunlu Kang, Weiyu Tao, Jiaxuan Xu, Xiaoyu Liu, Lei Chen","doi":"10.1101/2024.09.13.612767","DOIUrl":"https://doi.org/10.1101/2024.09.13.612767","url":null,"abstract":"Hepatitis B surface antigen (HBsAg), the only membrane protein on the HBV viral envelope, plays essential roles in HBV assembly, viral release, host cell attachment, and entry. It is also the target of neutralizing antibodies. Despite its functional and therapeutic importance, the detailed structure of HBsAg has remained enigmatic. Here, we present the core structure of HBsAg at 3.6 A resolution, determined using recombinant small spherical subviral particles (SVPs). The structure reveals how two HBsAg monomers interact to form a dimer, which is the basic building block of SVPs.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On the coupling between membrane bending and stretching in lipid vesicles 关于脂质囊泡中膜弯曲与拉伸之间的耦合关系
Pub Date : 2024-09-15 DOI: 10.1101/2024.09.13.612881
Håkan Wennerström, Emma Sparr, Joakim Stenhammar
The formation of a lipid vesicle from a lamellar phase involves a cost in bending energy of 100-1000 times the thermal energy for values of the membrane bending rigidity κ typical for phospholipid bilayers. The bending rigidity of a bilayer is however a strongly decreasing function of its thickness h, and the bilayer can thus reduce its bending energy by stretching (and thus thinning) the bilayer. In this paper, we construct a simple model to describe this mechanism for the coupling between bending and stretching and analyse its effect on the bending energy and thermal fluctuations of spherical lipid vesicles. We show that the bilayer thinning becomes significant for small vesicles, and for a vesicle with radius R0 ~ 15 nm there is a sizeable thinning of the bilayer compared to the planar state. We furthermore demonstrate how this thinning is associated with a significant decrease in free energy due to the thermally excited bending modes. We argue that this previously unexplored effect can explain the experimentally observed lower limit of achievable vesicle sizes, which eventually become unstable due to the thinning of the bilayer. We also sketch how this effect provides a potential generic mechanism for the strong curvature dependence of protein adsorption to lipid membranes.
在磷脂双分子层典型的膜弯曲刚度κ值下,从薄片相形成脂质囊泡所需的弯曲能是热能的 100-1000 倍。然而,双分子层的弯曲刚度是其厚度 h 的强烈递减函数,因此双分子层可以通过拉伸(从而变薄)来降低其弯曲能。在本文中,我们构建了一个简单的模型来描述这种弯曲与拉伸之间的耦合机制,并分析了它对球形脂质囊泡弯曲能和热波动的影响。我们的研究表明,对于小囊泡来说,双分子层变薄的现象非常明显,对于半径为 R0 ~ 15 nm 的囊泡来说,与平面状态相比,双分子层变薄的程度相当大。我们还进一步证明了这种减薄如何与热激发弯曲模式导致的自由能显著降低有关。我们认为,这种以前未曾探索过的效应可以解释实验观察到的可实现囊泡尺寸的下限,由于双分子层变薄,囊泡尺寸最终变得不稳定。我们还简述了这种效应如何为蛋白质吸附到脂膜上的强曲率依赖性提供了一种潜在的通用机制。
{"title":"On the coupling between membrane bending and stretching in lipid vesicles","authors":"Håkan Wennerström, Emma Sparr, Joakim Stenhammar","doi":"10.1101/2024.09.13.612881","DOIUrl":"https://doi.org/10.1101/2024.09.13.612881","url":null,"abstract":"The formation of a lipid vesicle from a lamellar phase involves a cost in bending energy of 100-1000 times the thermal energy for values of the membrane bending rigidity κ typical for phospholipid bilayers. The bending rigidity of a bilayer is however a strongly decreasing function of its thickness h, and the bilayer can thus reduce its bending energy by stretching (and thus thinning) the bilayer. In this paper, we construct a simple model to describe this mechanism for the coupling between bending and stretching and analyse its effect on the bending energy and thermal fluctuations of spherical lipid vesicles. We show that the bilayer thinning becomes significant for small vesicles, and for a vesicle with radius R<sub>0</sub> ~ 15 nm there is a sizeable thinning of the bilayer compared to the planar state. We furthermore demonstrate how this thinning is associated with a significant decrease in free energy due to the thermally excited bending modes. We argue that this previously unexplored effect can explain the experimentally observed lower limit of achievable vesicle sizes, which eventually become unstable due to the thinning of the bilayer. We also sketch how this effect provides a potential generic mechanism for the strong curvature dependence of protein adsorption to lipid membranes.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
bioRxiv - Biophysics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1