{
  "abstract": "Macrophages phagocytose IgG-opsonized target cells by forming phagocytic synapses upon binding of IgG to Fcγ receptors (FcγR) expressed on the macrophage surface. However, binding requires accessibility of both IgG and FcγR within densely packed glycocalyces that decorate the macrophage and target cell surfaces. Here, we use cell-like target particles to show that non-binding 'bystander' proteins not directly involved in phagocytic signaling can sterically interfere with FcγR engagement, ultimately inhibiting synapse formation and phagocytosis. Furthermore, we demonstrate that adding a tall binding protein to the target particle overcomes bystander-mediated inhibition and substantially recovers phagocytosis in a process we call kinetic enhancement. We confirm that tall binders are sufficient to drive short binder engagement in vitro and introduce theory and simulations to explain the nonmonotonic dependence of phagocytosis on tall binder surface density. These findings show that kinetic enhancement is a general and tunable feature of interface formation, providing a strategy for re-engineering transition states to promote short receptor engagement at cell-cell contacts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Bioengineering, University of California Berkeley, Berkeley, CA, USA.",
    "UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA, USA.",
    "Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA.",
    "Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.",
    "Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.",
    "Department of Bioengineering, University of California Berkeley, Berkeley, CA, USA. fletch@berkeley.edu.",
    "UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA, USA. fletch@berkeley.edu.",
    "Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA. fletch@berkeley.edu.",
    "Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. fletch@berkeley.edu.",
    "Chan Zuckerberg Biohub, San Francisco, CA, USA. fletch@berkeley.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Aymeric Chorlay"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Aaron M Joffe"
    },
    {
      "affs": [
        2
      ],
      "name": "Jared Huzar",
      "orcid": "0000-0001-5085-0554"
    },
    {
      "affs": [
        3
      ],
      "name": "Jaffar Hasnain"
    },
    {
      "affs": [
        0
      ],
      "name": "Caitlin E Cornell"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Phillip L Geissler",
      "orcid": "0000-0003-0268-6547"
    },
    {
      "affs": [
        5,
        6,
        7,
        8,
        9
      ],
      "name": "Daniel A Fletcher",
      "orcid": "0000-0002-1890-5364"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c8s88516k68s3.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78095-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13720194",
  "id": "c8s88516k68s3",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957709",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2403|Phagocytosis and Immune Regulation"
    ]
  ],
  "openalex": "W7214631534",
  "pdf_url": "https://europepmc.org/articles/PMC13720194?pdf=render",
  "pmcid": "PMC13720194",
  "pmid": "42957709",
  "published": "2026-09-28",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/c8s88516k68s3.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:44Z",
      "native_id": "MED:42957709",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957709"
    },
    {
      "first_seen": "2026-11-02T12:24:01Z",
      "native_id": "PMC13720194",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78095-7"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Phagocytosis and Immune Regulation",
      "subfield": "immunology"
    }
  ],
  "title": "Tall adhesions overcome cell surface steric interference and rescue antibody-dependent phagocytosis in macrophages.",
  "title_text": "Tall adhesions overcome cell surface steric interference and rescue antibody-dependent phagocytosis in macrophages.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:07Z",
  "url": "https://research.draconitic.com/paper/c8s88516k68s3",
  "venue": "Nature communications",
  "versions": []
}