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Aptamer Conformational Dynamics Modulate Neurotransmitter Sensing in Nanopores
Annina Stuber1, Ali Douaki2, Julian Hengsteler1
1Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, Zürich CH-8092, Switzerland.
ACS Nano
|September 18, 2023
Summary
Structure-switching aptamers in nanopores enable sensitive detection of small molecules like dopamine and serotonin. Their conformational changes alter ionic flow, providing distinct electronic signals for each neurotransmitter.
Area of Science:
- Biomimetic Nanotechnology
- Molecular Sensing
- Nanoscale Biophysics
Background:
- Aptamers undergo conformational changes upon binding small molecules, influencing ionic flux in nanopores.
- Understanding biomolecular interactions in confined nanoscale environments is crucial but limited.
- Structure-switching aptamer-modified nanopores offer potential for sensitive analyte detection.
Purpose of the Study:
- To elucidate the fundamental mechanisms of small-molecule detection in aptamer-modified nanopores.
- To correlate experimental findings with theoretical models for nanoscale sensing.
- To investigate the distinct electronic behaviors of dopamine and serotonin sensors.
Main Methods:
- Fabrication of dopamine and serotonin aptamer-functionalized nanopore sensors.
- Femtomolar detection limit assessment.
- Quartz crystal microbalance with dissipation monitoring (QCM-D).
- Finite element method (FEM) and molecular dynamics (MD) simulations.
Main Results:
- Dopamine and serotonin sensors exhibited opposite electronic responses despite similar mass and charge.
- Structure-switching mechanisms of individual aptamers directly correlated with sensor behavior.
- Experimental data were consistent with theoretical simulations.
Conclusions:
- The sensing mechanism in aptamer-modified nanopores is governed by aptamer structure-switching.
- This study enhances understanding of nanoscale confined biomolecular interactions.
- Findings drive innovation in biomimetic nanopore technologies for analyte detection.
