Protein Corona Selectivity on Carbon Nanotube Biosensors is Driven by Surface Coating and Chirality
Year: 2026
Type: preprint
Abstract: Semiconducting single-walled carbon nanotubes (SWCNTs) are versatile near-infrared fluorophores that are engineered to create sensors displaying modulated fluorescence upon interaction with target analytes. SWCNT properties depend on both surface functionalization and underlying lattice structure, defined by the chiral indices ( n , m ), enabling the development of wavelength-tunable nanosensors for biological research and diagnostic applications. While the principles of specific SWCNT surface modification with biomacromolecules have been widely investigated, the impact of surface chemistry and nanotube structure on protein interactions in complex biological fluids remains underexplored. Here, we investigated the role of SWCNT surface coating and chirality in protein corona formation in human blood plasma using mass spectrometry–based proteomics. We systematically compared protein corona formation across single-stranded (ssDNA)- and PEG-phospholipid-coated SWCNTs, as well as across nanotube chiralities ranging from (6,4) to (9,4). Our findings indicate that surface coating identity is the dominant factor governing differential protein adsorption. SWCNTs coated with tight-binding ssDNA sequences exhibited greater protein-corona selectivity, preferentially enriching apolipoproteins and more internally structured proteins, whereas the PEG-phospholipid coating globally reduced, though did not eliminate, protein adsorption. Larger-diameter SWCNTs adsorbed proteins with lower secondary-structure content and greater molecular mass. Protein corona formation was further shaped by protein–protein cooperative binding effects in a SWCNT coating-dependent manner. Finally, molecular dynamics simulations provide mechanistic support for the experimental finding that proteins with higher glycine content display enhanced binding to (GT) 6 - compared to (TAT) 4 -coated SWCNTs through distinct glycine-peptide binding modes. These insights provide a framework for the rational design of SWCNT-based sensors for protein-profile recognition in complex biological environments.
Source: ChemRxiv
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, Balgrist Stiftung, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fondation pour la Recherche Médicale, Eidgenössische Technische Hochschule Zürich, Universität Zürich, Functional Genomics Center Zurich, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: Learning and characterizing DNA sequences in DNA-nanotube hybrid structures for high-affinity binding and recognition of molecular targets, G4300801733, Integrative Engineering of Metal Oxide Nanohybrid-based Surgical Adhesives: From Particle Design to Performance Assessment by Multiscale Analytics, G8037759850
OpenAlex ID: W7125700282