Tiny Clusters for Big Impact in T Cell Activation

Le Saux, Guillaume; Nowakowski, Piotr; Toledo, Esti; Tzdaka, Sivan; Naaz, Shagufta; Segal, Yuval; Maman, Brit; Pandit, Jatin Jawhir; Iraqi, Muhammed; Yassin, Abed Al-Kader; Porgador, Angel; Smith, Ana-Sunčana; Schvartzman, Mark (2025) Tiny Clusters for Big Impact in T Cell Activation. Nano Letters, 25 (31). pp. 11878-11887. ISSN 1530-6984

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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.

Item Type:	Article
Uncontrolled Keywords:	T cell activation; antibody clustering; nanolithography; membrane fluctuation model
Subjects:	NATURAL SCIENCES > Physics > Biophysics and Medical Physics
Divisions:	Division of Physical Chemistry
Depositing User:	Dorijan Vulić
Date Deposited:	30 Jan 2026 09:33
URI:	http://fulir.irb.hr/id/eprint/11189
DOI:	10.1021/acs.nanolett.5c02361

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