{
  "abstract": "Toehold-mediated strand displacement (TMSD) is regarded as the simplest mechanism through which synthetic nucleicacid nanosystems can be dynamically actuated and is central to applications in biosensing, molecular computing, data storage and retrieval, and synthetic biology. In these implementations, TMSD often occurs in topologically-confined configurations, with the toehold domain being linked to other elements that restrict its conformational freedom. However, the effect of topological confinement on the biophysics of TMSD remains largely unexplored. Here, we study TMSD in a simple, physiologically-encountered configuration in which the toehold domain is located in a DNA ‘bubble’, a region where the two strands of an otherwise continuous DNA duplex are dehybridised. We show that this topological confinement reduces the rate of TMSD by ∼1–3 orders of magnitude as a result of alterations to the TMSD free-energy landscape. We further demonstrate that hybridisation of a short DNA strand to the target complex–away from the toehold domain–speeds up TMSD, hence providing a route for allosteric modulation of the reaction rate. Our results highlight the substantial effect of topological confinement on TMSD. These effects must be considered in the optimal design of dynamic nanostructures and molecular reaction networks while offering convenient strategies for the fine-tuning and modulation of reaction rates.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry",
    "Imperial College London",
    "Department of Chemical Engineering and Biotechnology",
    "University of Cambridge",
    "Department of Bioengineering and Centre for Engineering Biology",
    "Living Systems Institute and Biomedical Physics, University of Exeter",
    "Institut für Physiologie",
    "Universität Bern"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Andrew Stannard",
      "orcid": "0000-0001-6283-667X"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Aditya Sengar",
      "orcid": "0000-0003-2223-5604"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Alexander H. Clowsley",
      "orcid": "0000-0001-9318-1557"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Christian Soeller",
      "orcid": "0000-0002-9302-2203"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Thomas E. Ouldridge",
      "orcid": "0000-0001-8114-8602"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Lorenzo Di Michele",
      "orcid": "0000-0002-1458-9747"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7sehg7cyear0x.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009472/v1",
  "fulltext_url": null,
  "id": "7sehg7cyear0x",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009472/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Advanced biosensing and bioanalysis techniques"
    ]
  ],
  "openalex": "W7214342659",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009472/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/7sehg7cyear0x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009472",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009472/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Advanced biosensing and bioanalysis techniques",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Topologically-constrained toehold-mediated strand displacement",
  "title_text": "Topologically-constrained toehold-mediated strand displacement",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/7sehg7cyear0x",
  "venue": "ChemRxiv",
  "versions": []
}