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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [3];  [2];  [1]
  1. Columbia Univ., New York, NY (United States)
  2. Memorial Sloan Kettering Cancer Center, New York, NY (United States). Immunology Program
  3. Brookhaven National Lab. (BNL), Upton, NY (United States). Center for Functional Nanomaterials (CFN)

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.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0012704
OSTI ID:
1562313
Alternate ID(s):
OSTI ID: 1606184
Report Number(s):
BNL-213752-2020-JAAM
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 40; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 47 works
Citation information provided by
Web of Science

References (29)

Polarization of the Golgi apparatus and the microtubule-organizing center within cloned natural killer cells bound to their targets. journal December 1983
Improving T Cell Expansion with a Soft Touch journal January 2017
Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing journal March 2016
Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage journal August 2013
DeconvolutionLab2: An open-source software for deconvolution microscopy journal February 2017
Micropatterning of costimulatory ligands enhances CD4+ T cell function journal May 2008
Mechanosensing in T Lymphocyte Activation journal January 2012
A Novel Model for IFN-γ–Mediated Autoinflammatory Syndromes journal January 2015
Mechanical regulation of cell function with geometrically modulated elastomeric substrates journal August 2010
Migration of T Cells on Surfaces Containing Complex Nanotopography journal September 2013
Opposing Effects of PKCθ and WASp on Symmetry Breaking and Relocation of the Immunological Synapse journal May 2007
High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography journal March 2016
Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells journal May 2009
Fiji: an open-source platform for biological-image analysis journal June 2012
Cross Talk between CD3 and CD28 Is Spatially Modulated by Protein Lateral Mobility journal December 2013
Cells lying on a bed of microneedles: An approach to isolate mechanical force journal January 2003
Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity journal January 2011
Substrate Rigidity Regulates Human T Cell Activation and Proliferation journal June 2012
Differential Depth Sensing Reduces Cancer Cell Proliferation via Rho-Rac-Regulated Invadopodia journal July 2017
Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells journal March 2019
Is the Mechanical Activity of Epithelial Cells Controlled by Deformations or Forces? journal December 2005
Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells journal October 1982
CD4+ T-cell synapses involve multiple distinct stages journal September 2011
Enhanced Activation and Expansion of T Cells Using Mechanically Soft Elastomer Fibers journal January 2018
CD28 and CD3 have complementary roles in T-cell traction forces journal January 2014
Isoelectric focusing in an ordered micropillar array journal July 2008
Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes journal March 2019
Antigen Recognition Is Facilitated by Invadosome-like Protrusions Formed by Memory/Effector T Cells journal March 2012
Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function journal October 2003

Cited By (1)

Mechanotransduction in T Cell Development, Differentiation and Function journal February 2020