Abstract
ABSTRACT: Bridging the gap between traditional immunology and nanoscale biophysics has proved more difficult than originally thought whereas for cell biology applications, super-resolution microscopy has already afforded a raft of new concepts. From neuronal segmentation to nuclear pores and the 3D structure of focal adhesions – nanoscopy has begun to illuminate the link between nanoscale organization and function. In the field of immunology, the explanation must typically go further, linking nanoscale biophysical phenomena to the manifestation of specific diseases, or the altered activity of specific immune cell subtypes in a bodily compartment. What follows is a summary of how nanoscopy has elucidated immunological function, and what might be achieved in the future to link quantifiable, nanoscale, biophysical phenomena with cell and tissue functionality. We explore where the gaps in our understanding are, and how they might be narrowed by microscopists, biophysicists and immunologists working together.
Highlights
We explore where the gaps in our understanding occur, and how they might be addressed
Archetypal immune synapses can be recapitulated through use of supported lipid bilayers (SLBs) loaded with peptide bound major histocompatibility complex (p-MHC) [2], or more through the use of activating antibodies bound to glass, directed at the T cell receptor [3, 4]
Cell biology has benefitted from the system as headway has been made in understanding the role of nanoscale molecular organization of the TCR [5,6,7], LFA-1 [8, 9], LAT [10, 11] and the nanoscale meshworks formed from fibers like actin [12]
Summary
Bridging the gap between traditional immunology and nanoscale biophysics has proved more difficult than originally thought. Molecular clustering is necessary for the structured formation of adhesions in T cells [24], and new nanoscopy techniques have allowed us to show that there are levels of organization beyond microscale adhesion clusters The dynamics of such clusters likely occur across many timescales, and while live cell PALM in the T cell synapse has provided important insights into nanocluster dynamics with temporal resolution of 1–2 s [10, 11, 25,26,27], fast dynamics will rely on the development of much faster localization imaging. New ways to validate the quality of super-resolution data [51, 52], could be built into the process of screening before image processing
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