Frontiers in Chemistry and Chemical Engineering

All multicellular systems deposit molecular assemblies in the spaces between their cells. This extracellular matrix (ECM) is essential to nearly every process that involves cellular cooperation. But the study of ECM has lagged behind that of its intracellular counterparts, due in large part to two properties that extracellular assemblies possess: they are comprised of complex glycans and are not protected by cell membranes. Those properties render ECM resistant to conventional genetics- and sequencing-based methods. In my talk, I will demonstrate how chemical biology and advanced imaging can accelerate the study of extracellular physiology and pathology, using two examples. The first will describe development of a cell-impermeable small molecule fluorophore that turns on upon binding glycans, enabling nonperturbative visualization of ECM structure in systems ranging from in vitro substrates to in vivo mouse mammary tumors. The second reports a glycan-directed ruthenium(II) complex for visualization of ECM by electron microscopy, and its use for the discovery of hitherto unseen intercellular linkages. I will conclude with a forward-looking discussion of opportunities presented by functional imaging and cryo-electron microscopy for interrogation of extracellular biology.