Ali H. Shaib, Abed Alrahman Chouaib, Rajdeep Chowdhury, Jonas Altendorf, Daniel Mihaylov, Chi Zhang, Donatus Krah, Vanessa Imani, Russell K. W. Spencer, Svilen Veselinov Georgiev, Nikolaos Mougios, Mehar Monga, Sofiia Reshetniak, Tiago Mimoso, Han Chen, Parisa Fatehbasharzad, Dagmar Crzan, Kim-Ann Saal, Mohamad Mahdi Alawieh, Nadia Alawar, Janna Eilts, Jinyoung Kang, Alireza Soleimani, Marcus Müller, Constantin Pape, Luis Alvarez, Claudia Trenkwalder, Brit Mollenhauer, Tiago F. Outeiro, Sarah Köster, Julia Preobraschenski, Ute Becherer, Tobias Moser, Edward S. Boyden, A. Radu Aricescu, Markus Sauer, Felipe Opazo, Silvio O. Rizzoli
{"title":"一步式纳米级扩展显微镜揭示单个蛋白质的形状","authors":"Ali H. Shaib, Abed Alrahman Chouaib, Rajdeep Chowdhury, Jonas Altendorf, Daniel Mihaylov, Chi Zhang, Donatus Krah, Vanessa Imani, Russell K. W. Spencer, Svilen Veselinov Georgiev, Nikolaos Mougios, Mehar Monga, Sofiia Reshetniak, Tiago Mimoso, Han Chen, Parisa Fatehbasharzad, Dagmar Crzan, Kim-Ann Saal, Mohamad Mahdi Alawieh, Nadia Alawar, Janna Eilts, Jinyoung Kang, Alireza Soleimani, Marcus Müller, Constantin Pape, Luis Alvarez, Claudia Trenkwalder, Brit Mollenhauer, Tiago F. Outeiro, Sarah Köster, Julia Preobraschenski, Ute Becherer, Tobias Moser, Edward S. Boyden, A. Radu Aricescu, Markus Sauer, Felipe Opazo, Silvio O. Rizzoli","doi":"10.1038/s41587-024-02431-9","DOIUrl":null,"url":null,"abstract":"<p>The attainable resolution of fluorescence microscopy has reached the subnanometer range, but this technique still fails to image the morphology of single proteins or small molecular complexes. Here, we expand the specimens at least tenfold, label them with conventional fluorophores and image them with conventional light microscopes, acquiring videos in which we analyze fluorescence fluctuations. One-step nanoscale expansion (ONE) microscopy enables the visualization of the shapes of individual membrane and soluble proteins, achieving around 1-nm resolution. We show that conformational changes are readily observable, such as those undergone by the ~17-kDa protein calmodulin upon Ca<sup>2+</sup> binding. ONE is also applied to clinical samples, analyzing the morphology of protein aggregates in cerebrospinal fluid from persons with Parkinson disease, potentially aiding disease diagnosis. This technology bridges the gap between high-resolution structural biology techniques and light microscopy, providing new avenues for discoveries in biology and medicine.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"30 1","pages":""},"PeriodicalIF":33.1000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"One-step nanoscale expansion microscopy reveals individual protein shapes\",\"authors\":\"Ali H. Shaib, Abed Alrahman Chouaib, Rajdeep Chowdhury, Jonas Altendorf, Daniel Mihaylov, Chi Zhang, Donatus Krah, Vanessa Imani, Russell K. W. Spencer, Svilen Veselinov Georgiev, Nikolaos Mougios, Mehar Monga, Sofiia Reshetniak, Tiago Mimoso, Han Chen, Parisa Fatehbasharzad, Dagmar Crzan, Kim-Ann Saal, Mohamad Mahdi Alawieh, Nadia Alawar, Janna Eilts, Jinyoung Kang, Alireza Soleimani, Marcus Müller, Constantin Pape, Luis Alvarez, Claudia Trenkwalder, Brit Mollenhauer, Tiago F. Outeiro, Sarah Köster, Julia Preobraschenski, Ute Becherer, Tobias Moser, Edward S. Boyden, A. Radu Aricescu, Markus Sauer, Felipe Opazo, Silvio O. Rizzoli\",\"doi\":\"10.1038/s41587-024-02431-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The attainable resolution of fluorescence microscopy has reached the subnanometer range, but this technique still fails to image the morphology of single proteins or small molecular complexes. Here, we expand the specimens at least tenfold, label them with conventional fluorophores and image them with conventional light microscopes, acquiring videos in which we analyze fluorescence fluctuations. One-step nanoscale expansion (ONE) microscopy enables the visualization of the shapes of individual membrane and soluble proteins, achieving around 1-nm resolution. We show that conformational changes are readily observable, such as those undergone by the ~17-kDa protein calmodulin upon Ca<sup>2+</sup> binding. ONE is also applied to clinical samples, analyzing the morphology of protein aggregates in cerebrospinal fluid from persons with Parkinson disease, potentially aiding disease diagnosis. This technology bridges the gap between high-resolution structural biology techniques and light microscopy, providing new avenues for discoveries in biology and medicine.</p>\",\"PeriodicalId\":19084,\"journal\":{\"name\":\"Nature biotechnology\",\"volume\":\"30 1\",\"pages\":\"\"},\"PeriodicalIF\":33.1000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1038/s41587-024-02431-9\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41587-024-02431-9","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
One-step nanoscale expansion microscopy reveals individual protein shapes
The attainable resolution of fluorescence microscopy has reached the subnanometer range, but this technique still fails to image the morphology of single proteins or small molecular complexes. Here, we expand the specimens at least tenfold, label them with conventional fluorophores and image them with conventional light microscopes, acquiring videos in which we analyze fluorescence fluctuations. One-step nanoscale expansion (ONE) microscopy enables the visualization of the shapes of individual membrane and soluble proteins, achieving around 1-nm resolution. We show that conformational changes are readily observable, such as those undergone by the ~17-kDa protein calmodulin upon Ca2+ binding. ONE is also applied to clinical samples, analyzing the morphology of protein aggregates in cerebrospinal fluid from persons with Parkinson disease, potentially aiding disease diagnosis. This technology bridges the gap between high-resolution structural biology techniques and light microscopy, providing new avenues for discoveries in biology and medicine.
期刊介绍:
Nature Biotechnology is a monthly journal that focuses on the science and business of biotechnology. It covers a wide range of topics including technology/methodology advancements in the biological, biomedical, agricultural, and environmental sciences. The journal also explores the commercial, political, ethical, legal, and societal aspects of this research.
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In summary, Nature Biotechnology is a comprehensive journal that covers both the scientific and business aspects of biotechnology. It strives to provide researchers with valuable research papers and news while also delivering important scientific advancements to the business community.