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 2013, 5:75–85. doi: 10.1002/wnan.1195
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