{
  "abstract": "Plasma membrane (PM) phospholipid asymmetry is a fundamental feature of eukaryotic cells that regulates signaling, trafficking, and cell fate. Whether it also controls passive diffusion across the PM remains unknown. Here, we show that phospholipid asymmetry is a critical determinant of PM permeability to hydrophobic molecules. Using genetic and biochemical approaches, we demonstrate that disruption of lipid asymmetry by the Ca2 +‐activated scramblase TMEM16F or apoptotic scramblase XKR8 profoundly alters the permeation and intracellular accumulation of diverse hydrophobic compounds, including widely used fluorescent probes, while preserving the barrier to membrane‐impermeable molecules. Lipid scrambling is sufficient to remodel membrane permeability to lipophilic molecules, alter membrane biophysical properties, and differentially affect their intracellular accumulation, suggesting selective regulation of passive diffusion rather than nonspecific membrane leakage. Physiological lipid scrambling during T cell activation was also accompanied by altered membrane permeability. Moreover, lipid asymmetry regulates the cellular entry of doxorubicin, 17β‐estradiol, and all‐trans retinoic acid. Together, our findings identify PM lipid asymmetry as a previously unrecognized regulator of membrane permeability and establish a link between membrane organization and molecular transport.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "The First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology Anhui Medical University Hefei China",
    "Innovative Institute of Tumor Immunity and Medicine (ITIM) Hefei China",
    "Cell Architecture Research Center Tongji Medical College Huazhong University of Science and Technology Wuhan China",
    "Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy Hefei China",
    "Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Medical University Hefei China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jieming Ping",
      "orcid": "0009-0002-0920-8441"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenliang Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jinnuo Xu",
      "orcid": "0009-0009-8771-6979"
    },
    {
      "affs": [
        1
      ],
      "name": "Mengyun Yang",
      "orcid": "0009-0003-3939-3518"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4,
        5
      ],
      "name": "Ning Wu",
      "orcid": "0000-0001-7485-0436"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1yzrpd6xd09wj.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78435",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696883/",
  "id": "1yzrpd6xd09wj",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78435",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Lipid Membrane Structure and Behavior"
    ]
  ],
  "openalex": "W7223567950",
  "pdf_url": "https://europepmc.org/articles/PMC13696883?pdf=render",
  "pmcid": "PMC13696883",
  "pmid": "42928505",
  "published": "2026-10-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1yzrpd6xd09wj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:09Z",
      "native_id": "PMC13696883",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78435"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928505",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928505"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Lipid Membrane Structure and Behavior",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Plasma Membrane Lipid Asymmetry Dynamically Regulates Passive Diffusion",
  "title_text": "Plasma Membrane Lipid Asymmetry Dynamically Regulates Passive Diffusion",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:08Z",
  "url": "https://research.draconitic.com/paper/1yzrpd6xd09wj",
  "venue": "Advanced Science",
  "versions": []
}