Single-Particle STORM Imaging Quantifies Coating Heterogeneity Among Cell Membrane-Coated Nanoparticles
- 1Syracuse University
Abstract
Cell membrane-coated nanoparticles (CNPs) are a potentially transformative biomimetic targeted-delivery platform, which can engage therapeutic targets through source-cell membrane protein functions or homotypic interactions. However, their therapeutic development is limited by the current inability to accurately resolve membrane coating completeness, and CNP particle-to-particle variation. Here, we introduce a STochastic Optical Reconstruction Microscopy (STORM)-based approach that resolves population composition and quantifies membrane coating coverage at the single-particle level. Applying it to dendritic cell membrane- and HeLa cell membrane-coated nanoparticles (DCmPs and HeLamPs), we revealed substantial heterogeneity within both particle types and a cell-type dependence of coating outcomes, corroborated by confocal imaging and flow cytometry. We also quantified membrane protein composition, including peptide major histocompatibility complex class I (pMHC-I) among DCmPs, and confirmed that DCmPs preferentially engaged antigen-specific T cells in coculture. This single-particle framework establishes a quantitative standard for CNP characterization, providing a foundation for quality control and rational design.
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BibTeX
@misc{blauserwilson2026singleparticle,
title = {{Single-Particle STORM Imaging Quantifies Coating Heterogeneity Among Cell Membrane-Coated Nanoparticles}},
author = {J. Blauser-Wilson and A. Zareein and S. Puth and S. S. Jadhav and R. Chen and A. M. Hernandez and A. A. Joseph and J. Zeng and J. L. Hougland and Y. Wu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.755175},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.755175v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Single-Particle STORM Imaging Quantifies Coating Heterogeneity Among Cell Membrane-Coated Nanoparticles
AU - J. Blauser-Wilson
AU - A. Zareein
AU - S. Puth
AU - S. S. Jadhav
AU - R. Chen
AU - A. M. Hernandez
AU - A. A. Joseph
AU - J. Zeng
AU - J. L. Hougland
AU - Y. Wu
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.755175
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.755175v1
AB - Cell membrane-coated nanoparticles (CNPs) are a potentially transformative biomimetic targeted-delivery platform, which can engage therapeutic targets through source-cell membrane protein functions or homotypic interactions. However, their therapeutic development is limited by the current inability to accurately resolve membrane coating completeness, and CNP particle-to-particle variation. Here, we introduce a STochastic Optical Reconstruction Microscopy (STORM)-based approach that resolves population composition and quantifies membrane coating coverage at the single-particle level. Applying it to dendritic cell membrane- and HeLa cell membrane-coated nanoparticles (DCmPs and HeLamPs), we revealed substantial heterogeneity within both particle types and a cell-type dependence of coating outcomes, corroborated by confocal imaging and flow cytometry. We also quantified membrane protein composition, including peptide major histocompatibility complex class I (pMHC-I) among DCmPs, and confirmed that DCmPs preferentially engaged antigen-specific T cells in coculture. This single-particle framework establishes a quantitative standard for CNP characterization, providing a foundation for quality control and rational design.
ER -