Investigative and clinical applications of synthetic immune synapses
ABSTRACT The immune synapse (IS) has emerged as a compelling model of cell-cell communication. This interface between a T cell and antigen-presenting cell (APC) serves as a key point in coordinating the immune response. A distinguishing feature of this interface is that juxtacrine signaling molecules form complex patterns that are defined at micrometer and submicrometer scales. Moreover, these patterns are highly dynamic. While cellular and molecular approaches have provided insight into the influence of these patterns on cell-cell signaling, replacing the APC with a synthetic, micro/nanoengineered surface promises a new level of sophistication to these studies. Micropatterning of multiple ligands onto a surface, for example, allowed the direct demonstration that T cells can sense and respond to microscale geometry of the IS. Supported lipid bilayers have captured the lateral mobility of natural ligands, allowing insight into this complex property of the cell-cell interface in model systems. Finally, engineered surfaces have allowed the study of forces and mechanosensing in T cell activation, an emerging area of immune cell research. In addition to providing new insight into biophysical principles, investigations into IS function may allow control over ex vivo T cell expansion. Bioreactors based on these concepts may find immediate application in enhancing cellular-based immunotherapy. WIREs Nanomed Nanobiotechnol 2012. doi: 10.1002/wnan.1195 For further resources related to this article, please visit the WIREs website.
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ABSTRACT: It is increasingly recognized that cell signaling, as a chemical process, must be considered at the local, micrometer scale. Micro- and nanofabrication techniques provide access to these dimensions, with the potential to capture and manipulate the spatial complexity of intracellular signaling in experimental models. This review focuses on recent advances in adapting surface engineering for use with biomolecular systems that interface with cell signaling, particularly with respect to surfaces that interact with multiple receptor systems on individual cells. The utility of this conceptual and experimental approach is demonstrated in the context of epithelial cells and T lymphocytes, two systems whose ability to perform their physiological function is dramatically impacted by the convergence and balance of multiple signaling pathways.Annual review of biomedical engineering 07/2013; 15(1):305-26. DOI:10.1146/annurev-bioeng-071811-150050 · 14.21 Impact Factor
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ABSTRACT: While the beneficial impact of modifying and/or targeting T lymphocytes is becoming increasingly accepted in the treatment of different diseases, the road towards cell-based immunotherapy is still long and winding. Major challenges that remain include, amongst others, the guidance and exquisite regulation of immune processes ex vivo. In part, this is due to the difficulties of simulating ex vivo the intimate cellular interactions that occur between T cells and antigen-presenting cells (APCs). The fate of T cells is not solely regulated by the presence of certain molecules on the surface of APCs but also by their density and spatial distribution on the micro- and nanometric scale. Moreover, mechanical properties of APCs and force-dependent conformational changes during the formation of an immunological synapse (IS; a highly organized supramolecular complex at the T cellAPC interface), play a crucial role in T cell fate regulation. Various different technical means have been developed to create APC substitutes that are able to simulate ex vivo signals originating from naturally occurring APCs. Here, we review the performance of APC surrogates and discuss their contribution to understanding mechanisms underlying the ability of T cells to perform the “intelligent” mission of acquiring, processing and responding to environmental information.Israel Journal of Chemistry 09/2013; 53(9-10):n/a-n/a. DOI:10.1002/ijch.201300060 · 2.22 Impact Factor