Work

Geometric Confinement in Solid-State Nanopores Enables Single-Molecule Discrimination of Ferritin Subunits and Translocation Bias

Year: 2026

Type: article

Abstract: Resolving intact (24-mer) ferritin from its heavy and light chain subunits at the single-molecule level has remained a fundamental challenge, owing to their near-identical sizes and complex structural heterogeneity. Here, we quantitatively probe ferritin compositional and dynamic heterogeneity using confinement-modulated solid-state nanopores. Under weak confinement (∼20 nm), intact ferritin is discriminated from individual subunits via volumetric scaling of current blockades and a pronounced free-energy penalty governing its capture kinetics. Furthermore, transitioning to strong confinement (∼10 nm) reveals intrinsic, subunit-specific transport dynamics driven by steric-mechanical coupling. Finally, applying semisupervised learning to mixed samples uncovers a strong accessibility-driven translocation bias, demonstrating that nanopore readouts report capture-accessible molecular populations rather than nominal bulk abundance. This establishes a quantitative, physically grounded framework for decoding complex protein assembly states and transient dynamics in heterogeneous environments.

Source: Nano Letters

DOI: 10.1021/acs.nanolett.6c00914

Authors: Chaoming Gu, Xin Zhu, Santosh Khatri, Navod Thyashan, Kamruzzaman Joty, Min Jun Kim

Institutions: Southern Methodist University, University of Oxford, Zhejiang University

Language: English

Topic: Nanopore and Nanochannel Transport Studies

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, Division of Chemical, Bioengineering, Environmental, and Transport Systems

Awards: Multimodal Label-Free Nanosensor for Single Virus Characterization and Content Analysis, G4468654015, G8404490938