Antibody binding reports spatial heterogeneities in cell membrane organization
Abstract The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the spatial heterogeneities of macromolecular crowding on...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38525-2 |
| _version_ | 1797822797661077504 |
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| author | Daniel P. Arnold Yaxin Xu Sho C. Takatori |
| author_facet | Daniel P. Arnold Yaxin Xu Sho C. Takatori |
| author_sort | Daniel P. Arnold |
| collection | DOAJ |
| description | Abstract The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the spatial heterogeneities of macromolecular crowding on live cell surfaces. In this work, we combine experiment and simulation to report crowding heterogeneities on reconstituted membranes and live cell membranes with nanometer spatial resolution. By quantifying the effective binding affinity of IgG monoclonal antibodies to engineered antigen sensors, we discover sharp gradients in crowding within a few nanometers of the crowded membrane surface. Our measurements on human cancer cells support the hypothesis that raft-like membrane domains exclude bulky membrane proteins and glycoproteins. Our facile and high-throughput method to quantify spatial crowding heterogeneities on live cell membranes may facilitate monoclonal antibody design and provide a mechanistic understanding of plasma membrane biophysical organization. |
| first_indexed | 2024-03-13T10:13:26Z |
| format | Article |
| id | doaj.art-4616b67756be4f9c8a5e830b90674e47 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T10:13:26Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-4616b67756be4f9c8a5e830b90674e472023-05-21T11:20:05ZengNature PortfolioNature Communications2041-17232023-05-0114111310.1038/s41467-023-38525-2Antibody binding reports spatial heterogeneities in cell membrane organizationDaniel P. Arnold0Yaxin Xu1Sho C. Takatori2Department of Chemical Engineering, University of California, Santa BarbaraDepartment of Chemical Engineering, University of California, Santa BarbaraDepartment of Chemical Engineering, University of California, Santa BarbaraAbstract The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the spatial heterogeneities of macromolecular crowding on live cell surfaces. In this work, we combine experiment and simulation to report crowding heterogeneities on reconstituted membranes and live cell membranes with nanometer spatial resolution. By quantifying the effective binding affinity of IgG monoclonal antibodies to engineered antigen sensors, we discover sharp gradients in crowding within a few nanometers of the crowded membrane surface. Our measurements on human cancer cells support the hypothesis that raft-like membrane domains exclude bulky membrane proteins and glycoproteins. Our facile and high-throughput method to quantify spatial crowding heterogeneities on live cell membranes may facilitate monoclonal antibody design and provide a mechanistic understanding of plasma membrane biophysical organization.https://doi.org/10.1038/s41467-023-38525-2 |
| spellingShingle | Daniel P. Arnold Yaxin Xu Sho C. Takatori Antibody binding reports spatial heterogeneities in cell membrane organization Nature Communications |
| title | Antibody binding reports spatial heterogeneities in cell membrane organization |
| title_full | Antibody binding reports spatial heterogeneities in cell membrane organization |
| title_fullStr | Antibody binding reports spatial heterogeneities in cell membrane organization |
| title_full_unstemmed | Antibody binding reports spatial heterogeneities in cell membrane organization |
| title_short | Antibody binding reports spatial heterogeneities in cell membrane organization |
| title_sort | antibody binding reports spatial heterogeneities in cell membrane organization |
| url | https://doi.org/10.1038/s41467-023-38525-2 |
| work_keys_str_mv | AT danielparnold antibodybindingreportsspatialheterogeneitiesincellmembraneorganization AT yaxinxu antibodybindingreportsspatialheterogeneitiesincellmembraneorganization AT shoctakatori antibodybindingreportsspatialheterogeneitiesincellmembraneorganization |