Tiny Clusters for Big Impact in T Cell Activation

The regulation of T cell activation via engineered arrays holds significant biomedical potential. While average antibody density is known to influence T cell activation, antibody clustering has shown limited benefits. This study challenges this perspective through combined experimental and theoretical approaches. By employing nanolithographically patterned arrays, we show that full T cell activation is achievable with a small number of densely packed antibody clusters─even at average densities where homogeneous or sparsely clustered distributions are insufficient for full activation. These results align with the membrane-fluctuation model that considers cooperative binding and mechanical feedback. Our findings highlight the importance of the spatial organization of activating ligands and provide a framework for designing improved T cell activation platforms for immunotherapy.

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Publication Details

Journal
Nano Letters
Published
2025-07-26
DOI
https://doi.org/10.1021/acs.nanolett.5c02361
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00

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article

Tiny Clusters for Big Impact in T Cell Activation

Abed Alkader Yassin, Ana‐Sunčana Smith, Jatin Jawhir Pandit, Mark Schvartzman et al.
Nano Letters
CAR-T cell therapy research
article

Tiny Clusters for Big Impact in T Cell Activation

Abed Alkader Yassin, Ana‐Sunčana Smith, Jatin Jawhir Pandit, Mark Schvartzman, Guillaume Le Saux, Angel Porgador, Piotr Nowakowski, Esti Toledo, Muhammed Iraqi, Shagufta Naaz, Sivan Tzdaka, Brit Maman, Yuval Segal
article en

Abstract

The regulation of T cell activation via engineered arrays holds significant biomedical potential. While average antibody density is known to influence T cell activation, antibody clustering has shown limited benefits. This study challenges this perspective through combined experimental and theoretical approaches. By employing nanolithographically patterned arrays, we show that full T cell activation is achievable with a small number of densely packed antibody clusters─even at average densities where homogeneous or sparsely clustered distributions are insufficient for full activation. These results align with the membrane-fluctuation model that considers cooperative binding and mechanical feedback. Our findings highlight the importance of the spatial organization of activating ligands and provide a framework for designing improved T cell activation platforms for immunotherapy.

Nano LettersVol. 25(31)
Ben-Gurion University of the Negev (IL), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Center for Nanoscale Science and Technology (US), Henan University of Engineering (CN), Ruđer Bošković Institute (HR), Pediatrics and Genetics (US)
Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Israel Science Foundation
Openalex Percentile: Top 73%
CAR-T cell therapy research
DOISourceOpenAlex
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Tiny Clusters for Big Impact in T Cell Activation — Abed Alkader Yassin, Ana‐Sunčana Smith, et al. · Nano Letters (2025) | TGRS Research Map | TGRS