Please use this identifier to cite or link to this item: doi:10.22028/D291-33155
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Title: Micropatterned soft hydrogels to study the interplay of receptors and forces in T cell activation
Author(s): Zhang, Jingnan
Zhao, Renping
Li, Bin
Farrukh, Aleeza
Hoth, Markus
Qu, Bin
del Campo Bécares, Aránzazu
Language: English
Title: Acta biomaterialia
Volume: 119
Startpage: 234
Endpage: 246
Publisher/Platform: Elsevier
Year of Publication: 2021
Publikation type: Journal Article
Abstract: The analysis of T cell responses to mechanical properties of antigen presenting cells (APC) is experimentally challenging at T cell-APC interfaces. Soft hydrogels with adjustable mechanical properties and biofunctionalization are useful reductionist models to address this problem. Here, we report a methodology to fabricate micropatterned soft hydrogels with defined stiffness to form spatially confined T cell/hydrogel contact interfaces at micrometer scale. Using automatized microcontact printing we prepared arrays of anti-CD3 microdots on poly(acrylamide) hydrogels with Young's Modulus in the range of 2 to 50 kPa. We optimized the printing process to obtain anti-CD3 microdots with constant area (50 µm2, corresponding to 8 µm diameter) and comparable anti-CD3 density on hydrogels of different stiffness. The anti-CD3 arrays were recognized by T cells and restricted cell attachment to the printed areas. To test functionality of the hydrogel-T cell contact, we analyzed several key events downstream of T cell receptor (TCR) activation. Anti-CD3 arrays on hydrogels activated calcium influx, induced rearrangement of the actin cytoskeleton, and led to Zeta-chain-associated protein kinase 70 (ZAP70) phosphorylation. Interestingly, upon increase in the stiffness, ZAP70 phosphorylation was enhanced, whereas the rearrangements of F-actin (F-actin clearance) and phosphorylated ZAP70 (ZAP70/pY centralization) were unaffected. Our results show that micropatterned hydrogels allow tuning of stiffness and receptor presentation to analyze TCR mediated T cell activation as function of mechanical, biochemical, and geometrical parameters.
DOI of the first publication: 10.1016/j.actbio.2020.10.028
URL of the first publication: http://www.sciencedirect.com/science/article/pii/S1742706120306176
Link to this record: hdl:20.500.11880/30474
http://dx.doi.org/10.22028/D291-33155
ISSN: 1878-7568
1742-7061
Date of registration: 28-Jan-2021
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Biophysik
NT - Chemie
Professorship: M - Prof. Dr. Markus Hoth
NT - Prof. Dr. Aránzazu del Campo
Collections:Die Universitätsbibliographie

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