Interface-edited solid-state NMR to study cell interfaces.

Cell membrane interfaces, including the glycocalyx, play a crucial role in regulating signaling and molecular interactions, yet their molecular composition remains challenging to study in intact cells. Existing techniques often require extensive sample preparation or lack specificity for probing interfacial components directly. Here, we introduce a solid-state nuclear magnetic resonance (ssNMR) tool to fingerprint the molecular structure of the cell glycocalyx in intact cells within their native environment, offering insights relevant to drug delivery, tissue engineering, and biomedical research. Building on Goldman-Shen cross-polarization (CP) experiments, which exploit proton spin diffusion to generate C spectra near cell membranes, our enhanced approach provides spectral information from the membrane interface and its surroundings, probing a region up to 10 nm. Using interface-edited CP (1D) and PDSD (2D) spectra, we demonstrate spectral fingerprints of the mammalian cell glycocalyx. This method opens new avenues for studying cell interfaces in a dehydrated yet native-like state, preserving membrane composition and advancing structural biology.