TY  - JOUR
AU  - Shaib, Ali H
AU  - Chouaib, Abed Alrahman
AU  - Chowdhury, Rajdeep
AU  - Altendorf, Jonas
AU  - Mihaylov, Daniel
AU  - Zhang, Chi
AU  - Krah, Donatus
AU  - Imani, Vanessa
AU  - Spencer, Russell K W
AU  - Georgiev, Svilen Veselinov
AU  - Mougios, Nikolaos
AU  - Monga, Mehar
AU  - Reshetniak, Sofiia
AU  - Mimoso, Tiago
AU  - Chen, Han
AU  - Fatehbasharzad, Parisa
AU  - Crzan, Dagmar
AU  - Saal, Kim-Ann
AU  - Alawieh, Mohamad Mahdi
AU  - Alawar, Nadia
AU  - Eilts, Janna
AU  - Kang, Jinyoung
AU  - Soleimani, Alireza
AU  - Müller, Marcus
AU  - Pape, Constantin
AU  - Alvarez, Luis
AU  - Trenkwalder, Claudia
AU  - Mollenhauer, Brit
AU  - Outeiro, Tiago F
AU  - Köster, Sarah
AU  - Preobraschenski, Julia
AU  - Becherer, Ute
AU  - Moser, Tobias
AU  - Boyden, Edward S
AU  - Aricescu, A Radu
AU  - Sauer, Markus
AU  - Opazo, Felipe
AU  - Rizzoli, Silvio O
TI  - One-step nanoscale expansion microscopy reveals individual protein shapes.
JO  - Nature biotechnology
VL  - 43
IS  - 9
SN  - 1087-0156
CY  - New York, NY
PB  - Springer Nature
M1  - DZNE-2025-01104
SP  - 1539 - 1547
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Microscopy, Fluorescence: methods
KW  - Calmodulin: chemistry
KW  - Parkinson Disease: cerebrospinal fluid
KW  - Nanotechnology: methods
KW  - Proteins: chemistry
KW  - Calcium: metabolism
KW  - Protein Conformation
KW  - Calmodulin (NLM Chemicals)
KW  - Proteins (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39385007
C2  - pmc:PMC7616833
DO  - DOI:10.1038/s41587-024-02431-9
UR  - https://pub.dzne.de/record/281357
ER  -