As a universal phenomenon, the self-assembly of proteins or small molecules to form nanofibrils in a cellular environment is indispensable for the well-being of cells. There have been reports about the spatiotemporal distribution of fluorescent small molecules instructed by the enzymatic process in an intracellular environment. However, due to the complexity of live cells, selective formation of xenogenous nanofibrils on mammalian cells gains little attention. Here we report a method to image enzyme-triggered self-assembly of small molecules in pericellular space, especially of cancer cells that overexpress phosphatases. After conjugating a fluorophore to a small D-peptide derivative with a phosphorylated tyrosine motif, we found that surface and secretory phosphatases of live cells would dephosphorylate this precursor to trigger the self-assembly of the hydrogelator and result in pericellular nanofibrils. This enzymatic procedure not only generates a reaction product (i.e., nanofibrils of hydrogelators) that is both intensely fluorescent and highly photo-stable, but also reveals the regional heterogeneity of pericellular enzymatic activity. Thus, combining fluorescent imaging and enzyme-instructed self-assembly of small D-peptide derivative in a cellular environment, this approach allows the evaluation of pericellular self-assembly, the selectivity, the dynamics and the localization of the nanofibrils outside the live cells, as well as the characterization of the activities of surface and secretory phosphatases of live cells.

Imaging pericellular enzyme-instructed self-assembly of small molecules on live cells

248th National Meeting (2014)

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