Cell-surface sensors for real-time probing of cellular environments

Center for Regenerative Therapeutics & Department of Medicine, Brigham & Women's Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA.
Nature Nanotechnology (Impact Factor: 34.05). 07/2011; 6(8):524-31. DOI: 10.1038/nnano.2011.101
Source: PubMed


The ability to explore cell signalling and cell-to-cell communication is essential for understanding cell biology and developing effective therapeutics. However, it is not yet possible to monitor the interaction of cells with their environments in real time. Here, we show that a fluorescent sensor attached to a cell membrane can detect signalling molecules in the cellular environment. The sensor is an aptamer (a short length of single-stranded DNA) that binds to platelet-derived growth factor (PDGF) and contains a pair of fluorescent dyes. When bound to PDGF, the aptamer changes conformation and the dyes come closer to each other, producing a signal. The sensor, which is covalently attached to the membranes of mesenchymal stem cells, can quantitatively detect with high spatial and temporal resolution PDGF that is added in cell culture medium or secreted by neighbouring cells. The engineered stem cells retain their ability to find their way to the bone marrow and can be monitored in vivo at the single-cell level using intravital microscopy.

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Available from: Jeffrey M Karp, Oct 06, 2015
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    • "It would be significant to report the viability, differentiation, and even cell functions.3, 113 One idea is to design a smart NP with sensors, which detects stimuli associated with cell viability and functions.114 The stimuli includes chemicals secreted during cell differentiation, physical contact with neighboring cells during stem cell engraftment, intercellular pH changes during cell death, and certain moleculesin the cell microenvironment that trigger stem cell differentiation.115 "
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    • "Because aptamers are small and change conformation upon binding of their target, they can be engineered so that specific binding releases a quencher or generates a FRET pair, thus reducing non-specific staining [143]. So far, aptamers have been used to label mesenchymal stem and progenitor cells ex vivo and to visualize them in mouse bone marrow following transplantation [143]. The small size of Fab fragments and aptamers is also potentially their main limitation: owing to limited availability of lysine residues for chromophore binding, they are often less bright than traditional antibodies. "
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