Selective Leaflet‐Anchored DNA Nanoprobes for Simultaneous Monitoring of Juxta‐Plasma Membrane Environments

Y Yao He J Jie Lin (Department of Oncology The Second Affiliated Hospital of Kunming Medical University Kunming China) F Fandi Wu Y Yong‐Hao Ma (Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan Province, Hunan University Changsha Hunan 410082 China) Z Zhaoyang Wang H Hui Wu Z Zhimin Wang N Nachuan Wen (Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province) Y Yutong Zhang (State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences) W Wenfei Guo (Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan Province, Hunan University Changsha Hunan 410082 China) Y Yulin Du W Weihong Tan (Institute of Molecular Medicine (IMM), Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Uremia Diagnosis and Treatment Center, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, School of Chemistry and Chemical Engineering) L Liping Qiu (Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province)

Abstract

Abstract The cell membrane functions as a bidirectional interface that coordinates the selective transport of substances and information between the interior and exterior of the cell. Simultaneous monitoring of both the inner and outer local environments surrounding this lipid bilayer is crucial for elucidating various cellular activities but significantly challenged by the lack of technologies capable of precisely engineering biosensing probes on both membrane leaflets. In this work, by developing fusogenic nanoliposomes with high cell fusion efficiency, we successfully anchored amphiphilic DNA tetrahedral probes onto the inner leaflet of the plasma membrane. By integrating this with the direct anchoring of amphiphilic probes on the outer leaflet, we achieved precise functionalization of both leaflets of the cell membrane, thus enabling simultaneous monitoring of localized targets within their respective juxta‐plasma membrane environments, avoiding signal contamination caused by the optical diffraction limit. Using selectively dual‐leaflet‐anchored tetrahedral DNAzyme probes, we revealed that the transmembrane ion channel SLC41A1 synergistically modulated the influx of Na + and the efflux of Mg 2+ in live cells. With a modular design, this membrane‐anchored DNA nanoplatform can be readily extended for the study of bilateral interface‐dominant cellular processes, shifting the paradigm toward a more localized and subtle perspective.

Article Details

Volume / Issue Vol. 64, Issue 24
Published June 10, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

Y

Yao He

J

Jie Lin

Department of Oncology The Second Affiliated Hospital of Kunming Medical University Kunming China

F

Fandi Wu

Y

Yong‐Hao Ma

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan Province, Hunan University Changsha Hunan 410082 China

Z

Zhaoyang Wang

H

Hui Wu

Z

Zhimin Wang

N

Nachuan Wen

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province

Y

Yutong Zhang

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences

W

Wenfei Guo

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan Province, Hunan University Changsha Hunan 410082 China

Y

Yulin Du

W

Weihong Tan

Institute of Molecular Medicine (IMM), Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Uremia Diagnosis and Treatment Center, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine, School of Chemistry and Chemical Engineering

L

Liping Qiu

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province