UW-Madison researchers have developed a novel method for selectively depleting high-abundance proteins from complex biological samples, such as human serum, to enhance the detection and characterization of low-abundance protein biomarkers. This method uses in situ synthesis of protein-encapsulating MOFs, particularly Zeolitic Imidazolate Framework-8 (ZIF-8), which forms selectively around high-abundance plasma proteins like HSA. By leveraging the specific surface chemistry interactions of these proteins with metal ions and organic linkers, the MOFs grow around the proteins, isolating them within their porous structures while leaving lower-abundance proteins in solution for proteomic analysis.
This selective encapsulation provides a streamlined, high-throughput, and gentle approach that reduces the need for costly, time-consuming depletion methods like immunoaffinity chromatography. The MOF-based method offers consistent depletion of abundant proteins without harsh elution steps, preserving the integrity of protein samples for both bottom-up and top-down mass spectrometry-based proteomics. The MOF material is easily dissolved under mild, MS-compatible conditions, allowing for easy recovery and analysis of encapsulated and unbound proteins, potentially in their native states.