自己駆動型顕微鏡が変性タンパク質凝集を捕捉(Smart microscope captures aggregation of misfolded proteins)

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2025-07-24 スイス連邦工科大学ローザンヌ校(EPFL)

EPFLの研究チームは、誤折りたたみタンパク質の凝集をリアルタイムで予測・解析できる自律型スマート顕微鏡を開発。蛍光画像をAIモデル(AEGON)が解析し、凝集予兆を検出すると自動でBrillouin顕微鏡を起動し、非侵襲的に生体力学的変化を測定。別モデル(IC-LINA)はラベルフリーで成熟凝集体を識別可能。この技術は神経変性疾患の病態解明や創薬に革新をもたらす可能性を持つ。

<関連情報>

自律型顕微鏡はタンパク質凝集の発生を検出するとともに、インテリジェントなブリルアン画像化を可能にします Self-driving microscopy detects the onset of protein aggregation and enables intelligent Brillouin imaging

Khalid A. Ibrahim,Camille Cathala,Carlo Bevilacqua,Lely Feletti,Robert Prevedel,Hilal A. Lashuel & Aleksandra Radenovic
Nature Communications  Published:24 July 2025
DOI:https://doi.org/10.1038/s41467-025-60912-0

自己駆動型顕微鏡が変性タンパク質凝集を捕捉(Smart microscope captures aggregation of misfolded proteins)

Abstract

The process of protein aggregation, central to neurodegenerative diseases like Huntington’s, is challenging to study due to its unpredictable nature and relatively rapid kinetics. Understanding its biomechanics is crucial for unraveling its role in disease progression and cellular toxicity. Brillouin microscopy offers unique advantages for studying biomechanical properties, yet is limited by slow imaging speed, complicating its use for rapid and dynamic processes like protein aggregation. To overcome these limitations, we developed a self-driving microscope that uses deep learning to predict the onset of aggregation from a single fluorescence image of soluble protein, achieving 91% accuracy. The system triggers optimized multimodal imaging when aggregation is imminent, enabling intelligent Brillouin microscopy of this dynamic biomechanical process. Furthermore, we demonstrate that by detecting mature aggregates in real time using brightfield images and a neural network, Brillouin microscopy can be used to study their biomechanical properties without the need for fluorescence labeling, minimizing phototoxicity and preserving sample health. This autonomous microscopy approach advances the study of aggregation kinetics and biomechanics in living cells, offering a powerful tool for investigating the role of protein misfolding and aggregation in neurodegeneration.

生物化学工学
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