{"id":458232,"date":"2020-10-22T08:03:53","date_gmt":"2020-10-22T12:03:53","guid":{"rendered":"http:\/\/www.rochester.edu\/newscenter\/?p=458232"},"modified":"2023-01-25T13:24:02","modified_gmt":"2023-01-25T18:24:02","slug":"finally-a-way-to-see-molecules-wobble-458232","status":"publish","type":"post","link":"https:\/\/www.rochester.edu\/newscenter\/finally-a-way-to-see-molecules-wobble-458232\/","title":{"rendered":"Finally, a way to see molecules \u2018wobble\u2019"},"content":{"rendered":"<div style=\"width: 75%; font-size: 150%; font-face: arial; font-weight: bold; line-height: 125%; margin-bottom: 0.5em;\">Microscopy breakthrough reveals how proteins behave in 3D, enabling new insights into cell behavior and disease progression.<\/div>\n<p>Six years ago, the Nobel Prize in chemistry was awarded to three scientists for finding ways to <a href=\"https:\/\/www.nobelprize.org\/prizes\/chemistry\/2014\/press-release\/\">visualize the pathways of individual molecules<\/a> inside living cells.<\/p>\n<p>Now, researchers at the <a href=\"https:\/\/www.rochester.edu\">University of Rochester<\/a> and the <a href=\"https:\/\/www.fresnel.fr\/spip\/?lang=en\">Fresnel Institute in France<\/a> have found a way to visualize those molecules in even greater detail, showing their position and orientation in 3D, and even how they wobble and oscillate. The work could shed invaluable insights into the biological processes involved, for example, when a cell and the proteins that regulate its functions react to the virus that causes COVID-19.<\/p>\n<p>\u201cWhen a protein changes shape, it exposes other atoms that enhance the biological process, so the change of shape of a protein has a huge effect on other processes inside the cell,\u201d says Sophie Brasselet, director of the Fresnel Institute, who collaborated with <a href=\"http:\/\/www.hajim.rochester.edu\/optics\/people\/faculty\/alonso_miguel\/index.html\">Miguel Alonso<\/a> and <a href=\"http:\/\/www.hajim.rochester.edu\/optics\/people\/faculty\/brown_thomas\/index.html\">Thomas Brown<\/a>, both professors of optics at Rochester.<\/p>\n<p>Nicknamed CHIDO&mdash;for \u201cCoordinate and Height super-resolution Imaging with Dithering and Orientation\u201d&mdash;the technology is described in a new paper published in <em><a href=\"https:\/\/www.nature.com\/articles\/s41467-020-19064-6\">Nature Communications<\/a><\/em>. Designed and built by lead authors Valentina Curcio, a PhD student in Brasselet\u2019s group, and Luis Aleman-Castaneda, a PhD student in Alonso\u2019s group, CHIDO is precise within \u201ctens of nanometers in position and a few degrees of orientation\u201d in determining the parameters of single molecules,\u201d the team reports.<\/p>\n<div class=\"pullquote\">\u201cThis is one of the beauties of optics. If you have a device that can <em>create<\/em> just about any polarization state, then you also have a device that can <em>analyze<\/em> just about any possible polarization state. \u201d&mdash;Thomas Brown, professor of optics<\/div>\n<p>Using a glass plate subjected to uniform stress all around its periphery, the device can create and extrapolate wavelength oscillations and changes in polarization that occur when molecules are observed in a fluorescence microscope. The new technology transforms the image of a single molecule into a distorted focal spot, the shape of which directly encodes more precise 3D information than previous measurement tools. In effect, CHIDO can produce beams that have every possible polarization state.<\/p>\n<p>\u201cThis is one of the beauties of optics,\u201d Brown says. \u201cIf you have a device that can <em>create<\/em> just about any polarization state, then you also have a device that can <em>analyze<\/em> just about any possible polarization state.\u201d<\/p>\n<figure id=\"attachment_458822\" aria-describedby=\"caption-attachment-458822\" style=\"width: 630px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020-09-30_Brown_stressed_window_076-630x378.jpg\" alt=\"stress engineered optical glass\" width=\"630\" height=\"378\" class=\"size-medium wp-image-458822\" srcset=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020-09-30_Brown_stressed_window_076-630x378.jpg 630w, https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020-09-30_Brown_stressed_window_076-193x117.jpg 193w, https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020-09-30_Brown_stressed_window_076-768x461.jpg 768w, https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020-09-30_Brown_stressed_window_076.jpg 1000w\" sizes=\"auto, (max-width: 630px) 100vw, 630px\" \/><figcaption id=\"caption-attachment-458822\" class=\"wp-caption-text\">Thomas Brown, professor of optics, holds a plate of glass that has been engineered for a new microscopy system that can image individual molecules in three dimensions as well as capture how they \u201cwobble.\u201d (University of Rochester photo \/ J. Adam Fenster)<\/figcaption><\/figure>\n<p>The glass plate originated in Brown\u2019s lab as part of his long interest in developing beams with unusual polarizations. Alonso, an expert on the theory of polarization, worked with Brown on ways to refine this \u201cvery simple but very elegant device\u201d and expand its applications. During a visit to Marseille, Alonso described the plate to Brasselet, an expert in novel instrumentation for fluorescence and nonlinear imaging. Brasselet immediately suggested its possible use in the microscopy techniques she was working on to image individual molecules.<\/p>\n<p>\u201cIt\u2019s been a very complementary team,\u201d Brasselet says.<\/p>\n<p><strong><\/p>\n<h3>20 years in the making<\/h3>\n<p><\/strong><\/p>\n<p>In 1873, Ernst Abbe stipulated that microscopes would never obtain better resolution than half the wavelength of light. That barrier stood until Nobel laureates Eric Betzig and William Moerner\u2014with their single-molecule microscopy\u2014and Stefan Hell\u2014with his stimulated emission depletion microscopy\u2014found ways to bypass it.<\/p>\n<p>\u201cDue to their achievements the optical microscope can now peer into the nanoworld,\u201d the Nobel committee reported in 2014.<\/p>\n<p>\u201cWhat was missing in that Nobel Prize and the work in subsequent years was the ability to not only accurately know the location of a molecule, but to be able to characterize its direction and especially its motion in three dimensions,\u201d Brown says.<\/p>\n<p>In fact, the solution Brown, Alonso, and Brasselet now describe had its origins 20 years ago.<\/p>\n<p>Starting in 1999, Brown and one of his PhD students, Kathleen Youngworth, began investigating unusual optical beams that displayed unusual patterns of optical polarization, the orientation of the optical wave.\u00a0Some of the beams exhibited a spoke-like radial pattern with intriguing properties.<\/p>\n<p>Youngworth demonstrated on a tabletop that, when tightly focused, the beams exhibited polarization components that pointed in almost any direction in three dimensions.<\/p>\n<p>Alexis Spilman Vogt, another PhD candidate, then worked with Brown on creating the same effects by applying stress to the edges of a glass cylinder. Brown\u2019s brother-in-law, Robert Sampson, a skilled\u00a0tool and die specialist, was called upon to fabricate some samples and fit them in metal rings for use with a confocal microscope.<\/p>\n<p>This involved heating both the glass and metal rings. \u201cMetal expands at a faster rate when you heat it than glass does,\u201d Brown says, \u201cand so you could heat the glass and metal up very hot, insert the glass in the middle of the metal, and as it cools down the metal would shrink and create a tremendous force on the periphery of the glass.\u201d<\/p>\n<p>Sampson inadvertently applied more stress than called for with one of the plates. As soon as his brother-in-law handed it to him, Brown knew the plate had unusual qualities. The Rochester group introduced the term \u201cstress engineered optic\u201d to describe the elements and, as they learned more about both the physical behavior and the mathematics, they realized that the windows could be the path the solving entirely new problems in microscopy.<\/p>\n<p>And that was the origin of what is now CHIDO, which, coincidently, happens to be Mexican slang for \u201ccool.\u201d<\/p>\n<p>\u201cAt the time Alexis and I knew the stress-engineered glass was interesting, and would likely have useful applications; we just didn\u2019t know at the time what they might be,\u201d Brown says. Now, thanks to his collaboration with Alonso and Brasselet, he hopes CHIDO will \u201ccatch the imagination\u201d of other researchers in the field who can help further refine and apply the technology.<\/p>\n<p>The research was supported with funding from the National Science Foundation, the Excellence Initiative of Aix-Marseille University, the European Union\u2019s Horizon 2020 research and innovation program, and the CONACYT Doctoral Fellowship program.<\/p>\n<p><!-- begin copying for copy and paste--><\/p>\n<h3><strong>Read more<\/strong><\/h3>\n<div class=\"large-up-3\">\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.rochester.edu\/newscenter\/imaging-the-secret-lives-of-immune-cells-in-the-eye-455212\/\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/10\/2020_schallek-slide-2.jpg\" alt=\"image of cells\"><strong>Imaging the secret lives of immune cells in the eye<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">Rochester researchers demonstrate way to track the interactions of microscopic immune cells in a living eye without dyes or damage, a first for imaging science.<\/span><\/div>\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.rochester.edu\/newscenter\/rochester-researchers-document-record-setting-optical-fiber-453252\/\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/09\/2020_september_optical-fiber_2020-08-26_Renninger_lab_082.jpg\" alt=\"image of researchers in lab\"><br \/>\n<strong>Rochester researchers document record-setting optical fiber<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">Work shows the innovative fiber\u2014made of seven capillaries surrounding a hollow core\u2014may be a promising platform for quantum information processing and other applications.<\/span><\/div>\n<div class=\"column\" style=\"padding-left: 0px;\"><a href=\"https:\/\/www.rochester.edu\/newscenter\/rochester-labs-reopen-adapt-to-covid-19-precautions-in-innovative-ways-441882\/\"><img decoding=\"async\" style=\"margin-bottom: 10px;\" src=\"https:\/\/www.rochester.edu\/newscenter\/wp-content\/uploads\/2020\/06\/fea-research-restart.jpg\" alt=\"photo of four graduates on a 4-by-4 grid\" \/><br \/>\n<strong>As labs reopen, Rochester researchers adapt to COVID-19 precautions in innovative ways<\/strong><\/a><br \/>\n<span style=\"font-size: .9em;\">Time sharing, staggered shifts, and reconfigured spaces are among the adaptations the University has made for research to resume.<\/span><\/div>\n<\/div>\n<p>&nbsp;<br \/>\n<!-- stop copying.--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Breakthrough by international optics team reveals how proteins behave in 3D, enabling new insights into cell behavior and disease progression<\/p>\n","protected":false},"author":286,"featured_media":458812,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[116],"tags":[37592,18632,18652,36892,31062],"class_list":["post-458232","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sci-tech","tag-covid-19","tag-hajim-school-of-engineering-and-applied-sciences","tag-institute-of-optics","tag-research","tag-thomas-brown"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Finally, a way to see molecules \u2018wobble\u2019<\/title>\n<meta name=\"description\" content=\"University of Rochester optics faculty teams with French optical scientists to develop a way to visualize how proteins behave in 3D.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, 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