NeoMProbe: a new class of fluorescent cellular and tissue membrane probe

Chem Sci. 2024 Oct 30. doi: 10.1039/d4sc06225f. Online ahead of print.

Abstract

The development of long-lasting plasma membrane (PM) and basement membrane (BM) probes is in high demand to advance our understanding of membrane dynamics during differentiation and disease conditions. Herein, we report that the microheterogeneity of heparan sulfate (HS) on fluorescent neo-proteoglycans backbone offers a facile platform for designing membrane probes. Confocal live-cell imaging studies of cancer and normal cell lines with a panel of Cy5 fluorescently tagged neo-proteoglycans confirmed that highly sulfated HS ligands with an l-iduronic acid component (PG@ID-6) induce a prolonged and brighter expression on the PM compared to low-sulfated and uronic acid counterparts. Mono- and multi-photon microscopic imaging of tissue sections with NeoMProbe (PG@ID-6) allowed mapping BM and demonstrated staining efficacy equivalent to antibodies against the BM components. Finally, in vivo, whole-body imaging of NeoMProbe and subsequent tissue section imaging confirmed versatile and efficient membrane mapping by the probe. Overall, NeoMProbe offers a novel toolkit for cell biology and tissue biomembrane imaging.