Skip to main content
    • Aa
    • Aa

Nanoengineering of Immune Cell Function

  • Keyue Shen (a1), Michael C Milone (a2), Michael L. Dustin (a3) and Lance Cameron Kam (a4)

T lymphocytes are a key regulatory component of the adaptive immune system. Understanding how the micro- and nano-scale details of the extracellular environment influence T cell activation may have wide impact on the use of T cells for therapeutic purposes. In this article, we examine how the micro- and nano-scale presentation of ligands to cell surface receptors, including microscale organization and nanoscale mobility, influences the activation of T cells. We extend these studies to include the role of cell-generated forces, and the rigidity of the microenvironment, on T cell activation. These approaches enable delivery of defined signals to T cells, a step toward understanding the cell-cell communication in the immune system, and developing micro/nano- and material- engineered systems for tailoring immune responses for adoptive T cell therapies.

Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

[1] O. J. Finn Cancer immunology,” New England Journal of Medicine, vol. 358, pp. 2704–15, 2008.

[2] N. N. Hunder H. Wallen J. Cao D. W. Hendricks J. Z. Reilly R. Rodmyre A. Jungbluth S. Gnjatic J. A. Thompson and C. Yee Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1,” New England Journal of Medicine, vol. 358, pp. 2698–703, 2008.

[3] C. H. June Adoptive T cell therapy for cancer in the clinic,“ Journal of Clinical Investigation, vol. 117, pp. 1466–76, 2007.

[5] L. M. Weiner Cancer immunotherapy–the endgame begins,“ New England Journal of Medicine, vol. 358, pp. 2664–5, 2008.

[6] M. E. Dudley J. R. Wunderlich J. C. Yang R. M. Sherry S. L. Topalian N. P. Restifo R.E. Royal U. Kammula D. E. White S. A. Mavroukakis L. J. Rogers G. J. Gracia S. A. Jones , D. P. Mangiameli M. M. Pelletier J. Gea-Banacloche , M. R. Robinson D. M. Berman , A. C. Filie A. Abati and S. A. Rosenberg Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma,“ Journal of Clinical Oncology, vol. 23, pp. 2346–57, 2005.

[7] S. R. Riddell and P. D. Greenberg The use of anti-CD3 and anti-CD28 monoclonal antibodies to clone and expand human antigen-specific T cells,“ Journal of Immunoogicall Methods, vol. 128, pp. 189201, 1990.

[8] S. A. Rosenberg N. P. Restifo J. C. Yang R. A. Morgan and M. E. Dudley Adoptive cell transfer: a clinical path to effective cancer immunotherapy,“ Nature Reviews Cancer, vol. 8, pp. 299308, 2008.

[10] J. T. Chang V. R. Palanivel I. Kinjyo F. Schambach A. M. Intlekofer A. Banerjee S. A. Longworth , K. E. Vinup P. Mrass J. Oliaro N. Killeen J. S. Orange S. M. Russell W. Weninger , and S. L. Reiner Asymmetric T lymphocyte division in the initiation of adaptive immune responses,“ Science, vol. 315, pp. 1687–91, 2007.

[11] M. L. Dustin Hunter to gatherer and back: immunological synapses and kinapses as variations on the theme of amoeboid locomotion,“ Annual Review of Cell and Developmental Biology, vol. 24, pp. 577–96, 2008.

[12] M. L. Dustin and D. R. Colman Neural and immunological synaptic relations,“ Science, vol. 298, pp. 785–9, 2002.

[13] M. L. Dustin M. W. Olszowy A. D. Holdorf J. Li S. Bromley N. Desai P. Widder F. Rosenberger , P. A. van der Merwe , P. M. Allen and A. S. Shaw A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts,“ Cell, vol. 94, pp. 667–77, 1998.

[15] T. J. Thauland Y. Koguchi S. A. Wetzel M. L. Dustin and D. C. Parker Th1 and Th2 cells form morphologically distinct immunological synapses,“ Journal of Immunology, vol. 181, pp. 393–9, 2008.

[16] A. Trautmann and S. Valitutti The diversity of immunological synapses,“ Current Opinion in Immunology, vol. 15, pp. 249–54, 2003.

[17] S. Y. Tseng M. Liu and M. L. Dustin CD80 cytoplasmic domain controls localization of CD28, CTLA-4, and protein kinase Ctheta in the immunological synapse,“ Journal of Immunology, vol. 175, pp. 7829–36, 2005.

[18] S. Y. Tseng J. C. Waite M. Liu S. Vardhana and M. L. Dustin T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase C theta,“ Journal of Immunology, vol. 181, pp. 4852–63, 2008.

[19] J. Doh and D. J. Irvine Immunological synapse arrays: patterned protein surfaces that modulate immunological synapse structure formation in T cells,“ Proceedings of the National Academy of Sciences of the United States of America, vol. 103, pp. 5700–5, 2006.

[20] W. Senaratne P. Sengupta V. Jakubek D. Holowka C. K. Ober and B. Baird Functionalized surface arrays for spatial targeting of immune cell signaling,“ Journal of the American Chemical Society, vol. 128, pp. 5594–5, 2006.

[21] K. Shen V. K. Thomas M. L. Dustin and L. C. Kam Micropatterning of costimulatory ligands enhances CD4+ T cell function,“ Proceedings of the National Academy of Sciences of the United States of America, vol. 105, pp. 7791–6, 2008.

[22] K. Shen J. Qi and L. C. Kam Microcontact printing of proteins for cell biology,“ Journal of Visualized Experiments, 2008.

[23] A. J. Engler S. Sen H. L. Sweeney and D. E. Discher Matrix elasticity directs stem celllineage specification,“ Cell, vol. 126, pp. 677–89, 2006.

[24] G. Giannone and M. P. Sheetz Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways,“ Trends in Cell Biology, vol. 16, pp. 213–23, 2006.

[25] R. J. Pelham Jr. and Y. Wang Cell locomotion and focal adhesions are regulated by substrate flexibility,“ Proceedings of the National Academy of Sciences of the United States of America, vol. 94, pp. 13661–5, 1997.

[26] G. Jiang A. H. Huang Y. Cai M. Tanase and M. P. Sheetz Rigidity sensing at the leading edge through alphavbeta3 integrins and RPTPalpha,“ Biophysical Journal, vol. 90, pp. 1804–9, 2006.

[27] N. S. Astrof A. Salas M. Shimaoka J. Chen and T. A. Springer Importance of force linkage in mechanochemistry of adhesion receptors,“ Biochemistry, vol. 45, pp. 15020–8, 2006.

[28] G. Campi R. Varma and M. L. Dustin Actin and agonist MHC-peptide complexdependent T cell receptor microclusters as scaffolds for signaling,“ Journal of Experimental Medicine, vol. 202, pp. 10311036, 2005.

[29] B. A. Freiberg H. Kupfer W. Maslanik J. Delli J. Kappler D. M. Zaller and A. Kupfer Staging and resetting T cell activation in SMACs,“ Nature Immunology, vol. 3, pp. 911–7, 2002.

[30] M. F. Krummel M. D. Sjaastad C. Wulfing and M. M. Davis Differential clustering of CD4 and CD3zeta during T cell recognition,“ Science, vol. 289, pp. 1349–52, 2000.

[31] J. B. Huppa M. Gleimer C. Sumen and M. M. Davis Continuous T cell receptor signaling required for synapse maintenance and full effector potential,“ Nature Immunology, vol. 4, pp. 749–55, 2003.

[32] S. Valitutti M. Dessing K. Aktories H. Gallati and A. Lanzavecchia Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cellactin cytoskeleton,“ Journal of Experimental Medicine, vol. 181, pp. 577–84, 1995.

[34] T. Ilani G. Vasiliver-Shamis , S. Vardhana A. Bretscher and M. L. Dustin T cell antigen receptor signaling and immunological synapse stability require myosin IIA,“ Nature Immunology, vol. 10, pp. 531–9, 2009.

[35] H. G. Dobereiner B. J. Dubin-Thaler , J. M. Hofman H. S. Xenias T. N. Sims G. Giannone , M. L. Dustin C. H. Wiggins and M. P. Sheetz Lateral membrane waves constitute a universal dynamic pattern of motile cells,“ Physical Review Letters, vol. 97, p. 038102, 2006.

[36] M. L. Dustin Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses,“ Current Opinion in Cell Biology, vol. 19, pp. 529–33, 2007.

[37] J. Tsai and L. Kam Rigidity-dependent cross talk between integrin and cadherin signaling,“ Biophysical Journal, vol. 96, pp. L3941, 2009.

[38] Y. Dori H. Bianco-Peled , S. K. Satija G. B. Fields J. B. McCarthy and M. Tirrell Ligand accessibility as means to control cell response to bioactive bilayer membranes,“ Journal of Biomedical Materials Research, vol. 50, pp. 7581, 2000.

[39] A. Grakoui S. K. Bromley C. Sumen M. M. Davis A. S. Shaw P. M. Allen and M. L. Dustin , “The immunological synapse: a molecular machine controlling T cell activation,“ Science, vol. 285, pp. 221–7, 1999.

[40] J. T. Groves and M. L. Dustin Supported planar bilayers in studies on immune cell adhesion and communication,“ Journal of Immunological Methods, vol. 278, pp. 1932, 2003.

[41] K. D. Mossman G. Campi J. T. Groves and M. L. Dustin Altered TCR signaling from geometrically repatterned immunological synapses,“ Science, vol. 310, pp. 1191–3, 2005.

[43] S. Pautot H. Lee E. Y. Isacoff and J. T. Groves Neuronal synapse interaction reconstituted between live cells and supported lipid bilayers,“ Nature Chemical Biology, vol. 1, p. 283, 2005.

[44] T. D. Perez W. J. Nelson S. G. Boxer and L. Kam E-Cadherin Tethered to Micropatterned Supported Lipid Bilayers as a Model for Cell Adhesion,“ Langmuir, vol. 21, pp. 11963–8, 2005.

[45] D. Stroumpoulis H. Zhang L. Rubalcava J. Gliem and M. Tirrell Cell adhesion and growth to Peptide-patterned supported lipid membranes,“ Langmuir, vol. 23, pp. 3849–56, 2007.

[46] T. Yokosuka W. Kobayashi K. Sakata-Sogawa , M. Takamatsu A. Hashimoto-Tane , M. L. Dustin , M. Tokunaga and T. Saito Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C theta translocation,“ Immunity, vol. 29, pp. 589601, 2008.

[47] P. Y. Chan M. B. Lawrence M. L. Dustin L. M. Ferguson D. E. Golan and T. A. Springer , “Influence of Receptor Lateral Mobility On Adhesion Strengthening Between Membranes Containing Lfa-3 and Cd2,“ Journal of Cell Biology;, vol. 115, pp. 245255, 1991.

[48] A. L. DeMond and J. T. Groves Interrogating the T cell synapse with patterned surfaces and photoactivated proteins,“ Current Opinion in Immunology, vol. 19, pp. 722–7, 2007.

[49] L. Kam and S. G. Boxer Cell adhesion to protein-micropatterned-supported lipid bilayer membranes,“ Journal of Biomedical Materials Research, vol. 55, pp. 487–95, 2001.

[50] R. N. Orth M. Wu D. A. Holowka H. G. Craighead and B. A. Baird Mast Cell Activation on Patterned Lipid Bilayers of Subcellular Dimensions,“ Langmuir, vol. 19, pp. 15991605, 2003.

[51] L. Kam and S. G. Boxer Formation of supported lipid bilayer composition arrays by controlled mixing and surface capture,“ Journal of the American Chemical Society, vol. 122, pp. 12901–2, 2000.

[52] L. Kam and S. G. Boxer Spatially selective manipulation of supported lipid bilayers by laminar flow: steps towards biomembrane microfluidics,“ Langmuir, vol. 19, pp. 1624–31, 2003.

[53] T. Yang E. E. Simanek and P. Cremer Creating addressable aqueous microcompartments above solid supported phospholipid bilayers using lithographically patterned poly(dimethylsiloxane) molds,“ Analytical Chemistry, vol. 72, pp. 2587–9, 2000.

[54] C. Yoshina-Ishii and S. G. Boxer Arrays of mobile tethered vesicles on supported lipid bilayers,“ Journal of the American Chemical Society, vol. 125, pp. 3696–7, 2003.

[55] B. L. Jackson and J. T. Groves Scanning probe lithography on fluid lipid membranes,“ Journal of the American Chemical Society, vol. 126, pp. 13878–9, 2004.

[56] S. Lenhert P. Sun Y. Wang H. Fuchs and C. A. Mirkin Massively parallel dip-pen nanolithography of heterogeneous supported phospholipid multilayer patterns,“ Small, vol. 3, pp. 71–5, 2007.

[57] J. Shi J. Chen and P. S. Cremer Sub-100 nm patterning of supported bilayers by nanoshaving lithography,“ Journal of the American Chemical Society, vol. 130, pp. 2718–9, 2008.

[58] K. Shen J. Tsai P. Shi and L. C. Kam Self-aligned supported lipid bilayers for patterning the cell-substrate interface,“ Journal of the American Chemical Society, vol. 131, pp. 13204–5, 2009.

[59] J. Tsai E. Sun Y. Gao J. C. Hone and L. C. Kam Non-Brownian diffusion of membrane molecules in nanopatterned supported lipid bilayers,“ Nano Letters, vol. 8, pp. 425–30, 2008.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

MRS Online Proceedings Library (OPL)
  • ISSN: -
  • EISSN: 1946-4274
  • URL: /core/journals/mrs-online-proceedings-library-archive
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 4 *
Loading metrics...

Abstract views

Total abstract views: 100 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st September 2017. This data will be updated every 24 hours.