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

## TL;DR

A new solid-state NMR method is introduced to study the molecular structure of cell membrane interfaces, like the glycocalyx, in intact cells.

## Contribution

A novel ssNMR technique is developed to probe the glycocalyx in intact cells with high specificity and spatial resolution.

## Key findings

- The method uses interface-edited CP and PDSD spectra to fingerprint the glycocalyx in mammalian cells.
- The approach probes up to 10 nm from the membrane interface in a native-like, dehydrated state.
- This tool preserves membrane composition and offers insights for drug delivery and biomedical research.

## Abstract

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 13C 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.

Cell membrane interfaces, including the glycocalyx, play a crucial role in regulating signaling processes, yet its molecular composition remains poorly understood due to a lack of tools for probing interfacial components in intact cells. Here, the authors present a solid-state nuclear magnetic resonance approach that selectively probes the glycocalyx and its surroundings, providing molecular-level insights into cell interfaces in their native extracellular environment.