气候变化领域集成服务门户(CCPortal): Nanoconfinement of microvilli alters gene expression and boosts T cell activation

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DOI	10.1073/pnas.2107535118
	Nanoconfinement of microvilli alters gene expression and boosts T cell activation
	Aramesh M.; Stoycheva D.; Sandu I.; Ihle S.J.; Zünd T.; Shiu J.-Y.; Forró C.; Asghari M.; Bernero M.; Lickert S.; Oxenius A.; Vogel V.; Klotzsch E.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:40
英文摘要	T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanism by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200-nm pores but not in 400-nm pores. Consequently, formation of TCR nanoclustered hotspots within 200-nm pores allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cell-surface interactions; Immunoengineering; Mechanobiology; Nanoconfinement; T cell microvilli
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238346
作者单位	Laboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland; Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, 8093, Switzerland; Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, Zürich, 8092, Switzerland; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 40402, Taiwan; Department of Chemistry, Stanford University, Stanford, CA 94305, United States; Tissue Electronics, Fondazione Istituto Italiano di Tecnologia, Naples, 53-80125, Italy; Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, 8093, Switzerland; Institute for Biology, Experimental Biophysics/Mechanobiology, Humboldt University of Berlin, Berlin, 10117, Germany
推荐引用方式 GB/T 7714	Aramesh M.,Stoycheva D.,Sandu I.,et al. Nanoconfinement of microvilli alters gene expression and boosts T cell activation[J],2021,118(40).
APA	Aramesh M..,Stoycheva D..,Sandu I..,Ihle S.J..,Zünd T..,...&Klotzsch E..(2021).Nanoconfinement of microvilli alters gene expression and boosts T cell activation.Proceedings of the National Academy of Sciences of the United States of America,118(40).
MLA	Aramesh M.,et al."Nanoconfinement of microvilli alters gene expression and boosts T cell activation".Proceedings of the National Academy of Sciences of the United States of America 118.40(2021).