Stable and Reversible Functionalization of the Native Phosphate Groups on Live Cells

The ability to label live cell surfaces has many applications ranging from in vivo monitoring of cell populations to diagnostics and use of cells as drugs. Thus far, most reported strategies to label cell surfaces are not broadly applicable or easy to use for any cell type as it has relied on engineering cells with artificial moieties or conjugations that may affect cellular function. We provide a general solution to this long-standing problem by developing two-sided functionalization of the phosphate moieties that are ubiquitous on all cells. We show one application of our chemical strategy as a general-purpose live-cell membrane imaging reagent with long-time stability. Our strategy is broadly applicable to imaging, sensing, drug delivery, bioengineering, diagnostics and cell therapy.