Research
Atomic force microscopy (AFM) enables the manipulation of individual molecules and particles, providing a powerful means to investigate supramolecular structures and interactions. We apply these approaches to nanomedicine design, single-molecule mechanochemistry, high-performance supramolecular materials, and the nanomechanics of polymers in condensed states. To address the challenges arising from this research, we expand the range of measurement environments and accessible signals, developing single-molecule techniques that connect molecular structure, mechanical response, and chemical change.

Selected Publications
- Song, Y.; Ma, Z.; Zhang, W. Manipulation of a Single Polymer Chain: From the Nanomechanical Properties to Dynamic Structure Evolution. Macromolecules 2022, 55 (11), 4177–4199.
- Zhang, W.; Hou, J.; Li, N.; Zhang, W. Application of Atomic Force Microscopy (AFM)-based Single-molecule Force Spectroscopy (SMFS) in Polymer Characterization. Acta Polymerica Sinica 2021, 52 (11), 1523–1546.
Nanomedicine Design and Development
Research questions. How do nanocarriers recognize, bind to, and cross cell membranes? How do surface modification, targeting ligands, and nonspecific interactions affect delivery efficiency? We investigate how the behavior of nanomedicines at biological interfaces relates to their therapeutic function.
Our approach. We combine single-molecule force spectroscopy, single-particle force tracing, and biological imaging to measure binding forces and track endocytosis at the level of individual particles. We design peptide micelles, virus-like particles, nucleic acid nanostructures, and cell membrane-coated carriers to investigate drug loading, transmembrane transport, intracellular release, and nucleic acid delivery. In tumor models, we explore combinations of chemotherapy, phototherapy, gas therapy, gene silencing, and immunomodulation. We also develop antibacterial systems assisted by nucleic acid nanostructures and evaluate their performance in cell and animal models.
Selected Publications
- Xu, F.; Li, N.; Zhang, W.; Zhang, W. Force Spectroscopy-Assisted Design of DNAzyme-Loaded Virus-Like Particle System for Synergistic Combination Therapy of Breast Cancer. CCS Chem. 2026, 1–18 (ASAP).
- Li, N.; Xu, F.; Zhang, W.; Zhang, W. Bioinspired membrane-fusogenic nanomicelles for synergistic chemotherapy, photodynamic therapy, and gas therapy of breast cancer. Mater. Today Bio 2026, 36, 102681.
- Hou, J.; Li, N.; Zhang, W.; Zhang, W. Exploring the impact of PEGylation on the cell-nanomicelle interactions by AFM-based single-molecule force spectroscopy and force tracing. Acta Biomater. 2023, 157, 310–320.
- Zhang, Y.; Feng, W.; Zhang, W. Tetrahedral DNA Enhanced Antibacterial Effect of Lysozyme. ACS Mater. Lett. 2024, 6 (6), 2409–2415.
Single-Molecule Mechanochemistry and High-Performance Supramolecular Materials
Research questions. How does mechanical force change molecular conformations, regulate interactions, and drive chemical reactions? How do anchoring structures at molecular–metal interfaces, ions, and local environments affect load transfer, failure, and reversibility? We seek to connect the behavior of individual molecules under force with macroscopic material properties.
Our approach. We use single-molecule force spectroscopy and theoretical calculations to study mechanophore activation, bond scission, and subsequent reactions, and to develop anchoring strategies that improve interfacial stability. We examine conformations and binding states under force in systems governed by host–guest recognition, coordination, and hydrogen bonding. By incorporating functional units such as crown ethers into polymers, we regulate energy dissipation and combine molecular measurements with macroscopic mechanical testing to develop supramolecular materials with high strength, toughness, and responsiveness to stimuli.
Selected Publications
- Mei, Q.; Ma, Z.; Zhang, W. Interfacial Gold-Gold Interactions Govern the Mechanical Stability of N-Heterocyclic Carbene Self-Assembled Monolayers. J. Am. Chem. Soc. 2026, 148 (17), 17581–17586.
- Liu, X.; Yao, R.; Sun, Z.; Zhang, H.; Yan, F.; Li, H.; Zhang, W. Single-Molecule Study Reveals Ion-Dependent Conformational Change and Nanomechanical Property of Crown Ether-Based Polymer. Macromolecules 2024, 57 (8), 3798–3806.
- Zhang, H.; Li, X.; Lin, Y.; Gao, F.; Tang, Z.; Su, P.; Zhang, W.; Xu, Y.; Weng, W.; Boulatov, R. Multi-modal mechanophores based on cinnamate dimers. Nat. Commun. 2017, 8 (1), 1147.
- Xue, Y.; Li, X.; Li, H.; Zhang, W. Quantifying thiol–gold interactions towards the efficient strength control. Nat. Commun. 2014, 5 (1), 4348.
Nanomechanics of Polymers in Condensed States
Research questions. How do chain chemistry, chain folding, molecular packing, and connectivity in amorphous regions jointly determine polymer mechanics? How does the motion of individual chains in crystalline and amorphous networks contribute to stress transfer and macroscopic deformation, including fiber yielding?
Our approach. We use AFM and single-molecule force spectroscopy to investigate chain mechanics in single crystals, spherulites, and fibers across crystalline, semicrystalline, and amorphous polymers. Pulling individual chains from single crystals allows us to probe chain folding, force-induced melting, sliding, and relaxation, and to assess the effects of conformation, crystal thickness, crystal form, and temperature. We also study chain migration, long-range correlations in chain motion, and load bearing by tie chains, combining nanomechanical measurements with macroscopic tensile tests to connect single-chain structure with material properties.
Selected Publications
- Song, Y.; Deng, Y.; Zhang, W. Quantitative characterization of chain folding in crystalline polymers. Polymer 2026, 364, 130638.
- Zhang, X.; Zhang, H.; Lu, S.; Song, Y.; Zhang, W. Direct Detection of the Chain Trajectory and Long-Range Correlation in Crystalline-Amorphous Polymer Networks by Single-Molecule Force Spectroscopy. Macromolecules 2025, 58 (12), 6170–6177.
- Ma, Z.; Yang, P.; Zhang, X.; Jiang, K.; Song, Y.; Zhang, W. Quantifying the Chain Folding in Polymer Single Crystals by Single-Molecule Force Spectroscopy. ACS Macro Lett. 2019, 8 (9), 1194–1199.
- Liu, K.; Song, Y.; Feng, W.; Liu, N.; Zhang, W.; Zhang, X. Extracting a Single Polyethylene Oxide Chain from a Single Crystal by a Combination of Atomic Force Microscopy Imaging and Single-Molecule Force Spectroscopy: Toward the Investigation of Molecular Interactions in Their Condensed States. J. Am. Chem. Soc. 2011, 133 (10), 3226–3229.
Developing New Single-Molecule Techniques
Research questions. AFM force spectroscopy primarily measures force and distance. How can we also obtain information on molecular structure, chemical change, and particle position during force application? We focus on correlating and synchronizing complementary signals at the single-molecule and single-particle levels.
Our approach. We combine AFM with infrared spectroscopy to develop a single-molecule force spectroscopy–infrared spectroscopy (SMFS–IR) system that couples optical modulation with force detection. Together with single-molecule force measurements in air, this approach enables correlated detection and assignment of mechanical and chemical signals during polymer mechanochemistry at the single-molecule level. We also develop integrated AFM–total internal reflection fluorescence microscopy (AFM–TIRF) for single-particle fluorescence imaging and spectroscopy, and use nanoscale chemical imaging to investigate phase separation in polymer materials.
Selected Publications and Patent
- Cao, X.; Wang, W.; Jiang, Y.; Feng, W.; Xu, S.; Xu, W.; Zhang, W. An atomic force microscopy and total internal reflection fluorescence microscopy correlated system (AFM–TIRF) for fluorescence imaging and spectroscopy of a single particle. Rev. Sci. Instrum. 2024, 95 (7), 073706.
- Zhang, W.; Ma, Z.; Jiang, Y.; Feng, W.; Song, Y. Single-Molecule Force Spectroscopy-Infrared Spectroscopy (SMFS-IR) Coupling Method and System, and Device. US Patent 12,320,826 B1, June 3, 2025.







