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Prospective Students Current Students Faculty & Staff Alumni Industry Start your application today Undergraduate Admissions Graduate Admissions Dual Degree Program Graduate applicants: Attend an info session and skip the application fee Search Trending Searches graduate admissions academic programs financial aid academic calendar maps & directions summer school Home News & Events Imaging technique shows new details of peptide structures Imaging technique shows new details of peptide structures Researchers at Washington University in St. Louis outline how they used a chemical probe to light up interlocking peptides. Their technique will help scientists differentiate synthetic peptides from toxic types found in Alzheimer’s disease Leah Shaffer  04.25.2024 Single-molecule orientation–localization microscopy captures fluorescence from Nile red molecules as they transiently bind to fibrils composed of engineered KFE8 peptides. (Image: Weiyan Zhou) Share Share on Facebook Share on Twitter Share on Linkedin Email A new imaging technique developed by engineers at Washington University in St. Louis can give scientists a much closer look at fibril assemblies, stacks of peptides like amyloid beta, most notably associated with Alzheimer’s disease. These cross-β fibril assemblies are also useful building blocks within designer biomaterials for medical applications, but their resemblance to their amyloid beta cousins, whose tangles are a symptom of neurodegenerative disease, is concerning. Researchers want to learn how different sequences of these peptides are linked to their varying toxicity and function, for both naturally occurring peptides and their synthetic engineered cousins. Now, scientists can get a close enough look at fibril assemblies to see there are notable differences in how synthetic peptides stack compared with amyloid beta. These results stem from a fruitful collaboration between lead author Matthew Lew, associate professor in the Preston M. Green Department of Electrical & Systems Engineering, and Jai Rudra, associate professor of biomedical engineering, in WashU's McKelvey School of Engineering.  “We engineer microscopes to enable better nanoscale measurements so that the science can move forward,” Lew said.  In a paper published in ACS Nano, Lew and colleagues outline how they used the Nile red chemical probe to light up cross-β fibrils. Their technique called single-molecule orientation–localization microscopy (SMOLM) uses the flashes of light from Nile red to visualize the fiber structures formed by synthetic peptides and by amyloid beta. The bottom line: these assemblies are much more complicated and heterogenous than anticipated. But that’s good news, because it means there’s more than one way to safely stack your proteins. With better measurements and images of fibril assemblies, bioengineers can better understand the rules that dictate how protein grammar affects toxicity and biological function, leading to more effective and less toxic therapeutics. First, scientists need to see the difference between them, something very challenging because of the tiny scale of these assemblies.  “The helical twist of these fibers is impossible to discern using an optical microscope, or even some super-resolution microscopes, because these things are just too small,” Lew said. With high-dimensional imaging technology developed in Lew’s lab the past couple years, they are able to see the differences. A typical fluorescence microscope uses florescent molecules as light bulbs to highlight certain aspects of a biological target. In the case of this work, they used one of those probes, Nile red, as a sensor for what was around it. As Nile red randomly explores its environment and collides with the fibrils, it emits flashes of light that they can measure to determine where the fluorescent probe is and its orientation. From that data, they can piece together the full picture of engineered fibrils that stack very differently from the natural ones like amyloid beta. Their image of these fibril assemblies made the cover of the ACS Nano and was put together by first author Weiyan Zhou, who color-coded the image based on where the Nile reds were pointing. The resulting image is a blueish, red flowing assembly of peptides that looks like a river valley. They plan to continue to develop techniques like SMOLM to open new avenues of studying biological structures and processes at the nanoscale. “We are seeing things you can’t see with existing technology,” Lew said.  Weiyan Zhou, Conor L O’Neill, Tianben Ding, Oumeng Zhang, Jai S Rudra, and Matthew D Lew. Resolving the Nanoscale Structure of β-Sheet Peptide Self-Assemblies Using Single-Molecule Orientation–Localization Microscopy. ACS Nano 2024 18 (12), 8798-8810.  https://doi.org/10.1021/acsnano.3c11771 This work was supported by the National Science Foundation under award number 2047517 to J.S.R. and by the National Institute of General Medical Sciences of the National Institutes of Health under grant number R35GM124858 to M.D.L. Click on the topics below for more stories in those areas Research Electrical & Systems Engineering Back to News Faculty in this story View Profile Matthew Lew Associate Professor You may also be interested in: Advancing robot autonomy in unpredictable environments Yiannis Kantaros will enable teams of robots to interact collaboratively, perceive and respond to their environment with a CAREER Award from the National Science Foundation. 06.10.2024 DEMIST artificial intelligence tool may enhance usability of medical images A deep-learning-based image denoising method developed by Abhinav Jha may improve detection of myocardial defects in low-count SPECT scans. 06.04.2024 Quantum physics may help lasers see through fog, aid in communications JT Shen to pioneer two-color quantum photonic laser with DARPA grant. 06.04.2024 Facebook Twitter LinkedIn Instagram YouTube Engineering Departments Biomedical Engineering Computer Science & Engineering Division of Engineering Education Electrical & Systems Engineering Energy, Environmental & Chemical Engineering Mechanical Engineering & Materials Science Sever Institute - professional degrees Technology & Leadership Center - training for industry Contact Us Washington University in St. Louis McKelvey School of Engineering MSC: 1100-122-303 1 Brookings Drive St. Louis, MO 63130-4899 Contact Us Resources COVID-19 Resources Canvas Directory Equity, Diversity & Inclusion Emergency Management Engineering IT Maps & Directions Make a Gift WebFAC / WebSTAC ©2024 Washington University in St. Louis. 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