{
  "abstract": "Multimodal single-cell analysis aims to elucidate cellular-level phenotype within heterogeneous cell populations. Advancements in single-cell proteomics (SCP) seek to deepen quantitative depth, coverage, and reproducibility for a robust view of functional cell state. However, broadly accessible multimodal approaches are poised to benefit from sample-preparation advancements upstream of the mass spectrometer. Here, we introduce ProteoParcel, a multimodal SCP platform for indexing upstream widefield single-cell images to downstream label-free, bottom-up proteomics. Parcels are spatially arrayed planar polyacrylamide gels patterned with microwells. Each parcel, containing one microwell and an abutting gel region, is designed to integrate the single-cell imaging and SCP analysis modes. First, for whole-cell imaging, each microwell isolates an intact, individual breast cancer cell (MCF-7). After imaging, cells are subjected to in-microwell chemical cell lysis, electro-injection of whole-cell lysate from the microwell into the abutting gel region, in-gel chemical fixation, and finally in-gel tryptic digestion prior to peptide extraction for SCP. Location-indexed parcels are independently releasable to confer single-cell resolution to downstream mass spectrometry. To ensure SCP-suitable proteome solubilization and trypsin/Lys-C digestion, we optimize cell lysis, electrophoresis, and gel pre-equilibration conditions within the gel. Using ProteoParcel, we identify over 1,400 protein species from single, imaged MCF-7 cells. Scrutiny of the gel preparation conditions confirms that hydrogel-lysate interactions introduce predictable, physicochemically interpretable (cell membrane, hydrophobicity) detection biases, while broad functional-class composition and subcellular compartment coverage are preserved when benchmarked to in-solution digestion. ProteoParcel makes facile same-cell multimodal SCP and live-cell imaging.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, Berkeley"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "M. Overton"
    },
    {
      "name": "C. Deroy"
    },
    {
      "name": "E. Wang"
    },
    {
      "name": "A. Lennon"
    },
    {
      "name": "J. E. Elias"
    },
    {
      "name": "R. McClure"
    },
    {
      "affs": [
        0
      ],
      "name": "A. E. Herr"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4xa1rfkd5ar1d.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.09.04.749469",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749469v1.full",
  "id": "4xa1rfkd5ar1d",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749469v1",
  "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",
      "bioengineering"
    ],
    [
      "openalex",
      "1607|Advanced Proteomics Techniques and Applications"
    ]
  ],
  "openalex": "W7212074060",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749469v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4xa1rfkd5ar1d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:37Z",
      "native_id": "10.64898/2026.09.04.749469",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.04.749469v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Arrayed hydrogels pair whole-cell imaging with single-cell mass spectrometry proteomics",
  "title_text": "Arrayed hydrogels pair whole-cell imaging with single-cell mass spectrometry proteomics",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:37Z",
  "url": "https://research.draconitic.com/paper/4xa1rfkd5ar1d",
  "venue": "bioRxiv",
  "versions": []
}