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Title: T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces

Abstract

Cells have the remarkable ability to sense the mechanical stiffness of their surroundings. This has been studied extensively in the context of cells interacting with planar surfaces, a conceptually elegant model that also has application in biomaterial design. However, physiological interfaces are spatially complex, exhibiting topographical features that are described over multiple scales. This report explores mechanosensing of microstructured elastomer surfaces by CD4 + T cells, key mediators of the adaptive immune response. We show that T cells form complex interactions with elastomer micropillar arrays, extending processes into spaces between structures and forming local areas of contraction and expansion dictated by the layout of microtubules within this interface. Conversely, cytoskeletal reorganization and intracellular signaling are sensitive to the pillar dimensions and flexibility. Unexpectedly, these measures show different responses to substrate rigidity, suggesting competing processes in overall T cell mechanosensing. The results of this study demonstrate that T cells sense the local rigidity of their environment, leading to strategies for biomaterial design.

Authors:
; ; ; ; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1562313
Grant/Contract Number:  
SC0012704
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 116 Journal Issue: 40; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

Citation Formats

Jin, Weiyang, Tamzalit, Fella, Chaudhuri, Parthiv Kant, Black, Charles T., Huse, Morgan, and Kam, Lance C. T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces. United States: N. p., 2019. Web. doi:10.1073/pnas.1906986116.
Jin, Weiyang, Tamzalit, Fella, Chaudhuri, Parthiv Kant, Black, Charles T., Huse, Morgan, & Kam, Lance C. T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces. United States. doi:10.1073/pnas.1906986116.
Jin, Weiyang, Tamzalit, Fella, Chaudhuri, Parthiv Kant, Black, Charles T., Huse, Morgan, and Kam, Lance C. Mon . "T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces". United States. doi:10.1073/pnas.1906986116.
@article{osti_1562313,
title = {T cell activation and immune synapse organization respond to the microscale mechanics of structured surfaces},
author = {Jin, Weiyang and Tamzalit, Fella and Chaudhuri, Parthiv Kant and Black, Charles T. and Huse, Morgan and Kam, Lance C.},
abstractNote = {Cells have the remarkable ability to sense the mechanical stiffness of their surroundings. This has been studied extensively in the context of cells interacting with planar surfaces, a conceptually elegant model that also has application in biomaterial design. However, physiological interfaces are spatially complex, exhibiting topographical features that are described over multiple scales. This report explores mechanosensing of microstructured elastomer surfaces by CD4 + T cells, key mediators of the adaptive immune response. We show that T cells form complex interactions with elastomer micropillar arrays, extending processes into spaces between structures and forming local areas of contraction and expansion dictated by the layout of microtubules within this interface. Conversely, cytoskeletal reorganization and intracellular signaling are sensitive to the pillar dimensions and flexibility. Unexpectedly, these measures show different responses to substrate rigidity, suggesting competing processes in overall T cell mechanosensing. The results of this study demonstrate that T cells sense the local rigidity of their environment, leading to strategies for biomaterial design.},
doi = {10.1073/pnas.1906986116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 40,
volume = 116,
place = {United States},
year = {2019},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1906986116

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