Non-destructive colocalization sensing of microRNAs and membrane proteins in single vesicles reveals spatial inflammation signatures
Abstract
Chronic inflammation underlies a broad spectrum of diseases, yet current liquid biopsy approaches lack the spatial resolution and molecular specificity to detect localized, disease-specific inflammatory signals. Extracellular vesicles (EVs) offer a promising alternative, as they carry both membrane proteins and intravesicular biomolecules that reflect the physiological state and tissue of origin. Here, we present a sensing platform for single-vesicle colocalization analysis of membrane proteins and microRNAs (miRNAs), using cellulose nanofiber-mediated membrane fusion to non-destructively deliver probes into intact EVs. This approach enables simultaneous detection of tissue-specific and inflammation-associated markers in individual EVs. In kidney transplant recipients with chronic active antibody-mediated rejection, we identify EVs co-expressing the renal marker DPYS and miR-1246. In rheumatoid arthritis patients, we observe elevated levels of miR-1246 + /CD81 + EVs in plasma. Our platform distinguishes among inflammation-related EV subpopulations that are undetectable using bulk or surface-only analyses, thereby offering a non-invasive strategy for localized inflammation profiling.
// Source
Authors: Shota Kawaguchi, Taiga Ajiri, Kunanon Chattrairat, Hirotaka Koga, Yukiko Kamiya, Fuminori Sato, Hiroyuki Asanuma, Masatoshi Maeki, Manabu Tokeshi, Takeshi Yokoyama, Yoshikazu Tanaka, Kosuke Yoshida, Akira Yokoi, Kiyohiko Hotta, Naoya Iwahara, Yuichiro Fujieda, Mitsutaka Yasuda, Tatsuya Atsumi, Shimpei I. Kubota, Kaoru Murakami, Masaaki Murakami, Takao Yasui
Institutions: The University of Osaka, Hokkaido University, Tohoku University, Nagoya University, Institute of Science Tokyo, Kobe Pharmaceutical University, National Institutes of Natural Sciences, National Institute for Physiological Sciences, National Institutes for Quantum Science and Technology