{
  "abstract": "Sterols are fundamental components of biological membranes that modulate membrane fluidity and organisation, yet their role in governing interfacial proton dynamics remains underexplored. Here, we elucidate how cholesterol (Ch) and cholesterol sulfate (ChS) regulate excited-state proton transfer (PT) and long-range proton diffusion (PD) using a complementary dual-approach experimental framework combined with molecular dynamics (MD) simulations. Using a membrane-anchored photoacid in small unilamellar vesicles, we demonstrate that Ch accelerates local PT dynamics in gel-phase phosphatidylcholine membranes by inducing a fluid, liquid-ordered phase. Surprisingly, ChS inhibits local PT despite its negative headgroup. MD simulations reveal this inhibition stems from deeper probe embedding within ChS containing bilayers and the reduced basicity of sulfate relative to phosphate. Conversely, solid-state electrical measurements on supported lipid bilayers show a stark reversal for long range proton conduction (lateral PD): ChS increases lateral proton conductance by 400 fold under controlled relative humidity, whereas Ch decreases conductivity. This divergence arises mainly because ChS supplies titratable sulfate charge carriers, whereas Ch dilutes key phosphate proton mediators that promote a percolating interfacial hydrogen bonding network without providing charge carriers. Our findings demonstrate that sterols exert scale-dependent control over membrane PT/PD, revealing how headgroup chemistry, membrane fluidity, and hydration synergistically govern bioenergetic proton dynamics.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Sheffield"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "A. R. Variyam"
    },
    {
      "name": "M. Rzycki"
    },
    {
      "name": "D. Drabik"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Amdursky"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/afj49ty1897xa.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.05.764480",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764480v1.full",
  "id": "afj49ty1897xa",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764480v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764480v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/afj49ty1897xa.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:21:18Z",
      "native_id": "10.64898/2026.11.05.764480",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.05.764480v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Opposing Roles of Cholesterol and Cholesterol Sulfate in Proton Transfer and Diffusion at Membrane Interfaces",
  "title_text": "Opposing Roles of Cholesterol and Cholesterol Sulfate in Proton Transfer and Diffusion at Membrane Interfaces",
  "type": "preprint",
  "updated_at": "2026-11-08T00:21:07Z",
  "url": "https://research.draconitic.com/paper/afj49ty1897xa",
  "venue": "bioRxiv",
  "versions": []
}