{
  "abstract": "Despite decades of development, the clinical translation of amphiphilic self‐assembled nanoparticles remains limited by the lack of a predictive molecular design framework, owing to the complex, dynamic behavior of nanoparticles and cell membranes. Here, we introduce a building‐block design strategy focused on amphiphile monomers rather than assembled nanoparticles, a critical distinction because nanoparticle morphology is not a fixed design parameter. This molecular framework links amphiphile chemical structure to programmable cellular interactions. Through predictive variation of headgroup and tail chemistries, we demonstrate that amphiphile design dictates nanoparticle fate at cell membranes. Fully fluorinated nanoparticles remain intact and adsorb onto the membrane surface, hydrocarbon nanoparticles rapidly dissociate and fuse, whereas semi‐fluorinated nanoparticles exhibit tunable kinetic delays, enabling programmable responses such as stability at rigid interfaces but dissociation at fluid membranes. Crucially, we identify the free energy of transfer (ΔG transfer)–the energetic difference between extracting an amphiphile from the nanoparticle and from the cell membrane–as a unified thermodynamic descriptor that accurately predicts behavior across simulations and experiments without requiring full‐system modeling. Collectively, this predictive, chemistry‐driven framework shifts the design paradigm from nanoparticle morphology to amphiphile chemistry, enabling the rational engineering of self‐assembled nanocarriers for targeted drug delivery and responsive drug release applications.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Polymer and Color Engineering Amirkabir University of Technology Tehran Iran",
    "Institut Für Chemie und Biochemie Organische Chemie Freie Universität Berlin Berlin Germany",
    "Department of Chemical Engineering Soft Matter Rheology and Technology KU Leuven Leuven Belgium",
    "Institut Für Chemie und Biochemie Forschungszentrum Für Elektronenmikroskopie Freie Universität Berlin Berlin Germany",
    "School of Biosciences Chanakya University Bengaluru India",
    "Department of Physics Freie Universitätät Berlin Berlin Germany",
    "Department of Chemistry and Materials Innovation Factory University of Liverpool Liverpool UK",
    "Department of Chemical Engineering University of Bath Bath UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mahsa Nami"
    },
    {
      "affs": [
        1
      ],
      "name": "Tiffany Guitton‐Spassky"
    },
    {
      "affs": [
        0
      ],
      "name": "Farhad Sharif"
    },
    {
      "affs": [
        1
      ],
      "name": "Natalie Hanheiser",
      "orcid": "0000-0002-1610-5072"
    },
    {
      "affs": [
        1
      ],
      "name": "Riensqia Saudale"
    },
    {
      "affs": [
        1
      ],
      "name": "Jannik Gabriel",
      "orcid": "0009-0005-5342-1807"
    },
    {
      "affs": [
        1
      ],
      "name": "Aarti"
    },
    {
      "affs": [
        2
      ],
      "name": "Alireza Mirzaalipour",
      "orcid": "0009-0003-3890-3467"
    },
    {
      "affs": [
        0
      ],
      "name": "MohammadJavad Hafezi"
    },
    {
      "affs": [
        3
      ],
      "name": "Boris Schade",
      "orcid": "0000-0002-9157-7897"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Abhishek Kumar Singh",
      "orcid": "0000-0002-8398-9947"
    },
    {
      "affs": [
        1
      ],
      "name": "Rainer Haag"
    },
    {
      "affs": [
        5
      ],
      "name": "Roland R. Netz",
      "orcid": "0000-0003-0147-0162"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Hesam Makki",
      "orcid": "0000-0003-4296-5022"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9jjdj9yg76kd3.bib",
  "cited_by": 0,
  "doi": "10.1002/smll.75376",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711464/",
  "id": "9jjdj9yg76kd3",
  "issns": [
    "1613-6810",
    "1613-6829"
  ],
  "landing_url": "https://doi.org/10.1002/smll.75376",
  "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": "W7203997192",
  "pdf_url": null,
  "pmcid": "PMC13711464",
  "pmid": "42631557",
  "published": "2026-08-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9jjdj9yg76kd3.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:14Z",
      "native_id": "PMC13711464",
      "source": "pmc",
      "url": "https://doi.org/10.1002/smll.75376"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Lipid Membrane Structure and Behavior",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Predictive Amphiphile Design Enables Control of Self‐Assembled Nanoparticle‐Cell Membrane Interactions",
  "title_text": "Predictive Amphiphile Design Enables Control of Self‐Assembled Nanoparticle‐Cell Membrane Interactions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:14Z",
  "url": "https://research.draconitic.com/paper/9jjdj9yg76kd3",
  "venue": "Small (Weinheim an Der Bergstrasse, Germany)",
  "versions": []
}