Boronic Acid-Rich Lanthanide Metal-Organic Frameworks Enable Deep Proteomics with Ultratrace Biological Samples

Adv Mater. 2024 Aug;36(33):e2401559. doi: 10.1002/adma.202401559. Epub 2024 Jul 3.

Abstract

Label-free proteomics is widely used to identify disease mechanism and potential therapeutic targets. However, deep proteomics with ultratrace clinical specimen remains a major technical challenge due to extensive contact loss during complex sample pretreatment. Here, a hybrid of four boronic acid-rich lanthanide metal-organic frameworks (MOFs) with high protein affinity is introduced to capture proteins in ultratrace samples jointly by nitrogen-boronate complexation, cation-π and ionic interactions. A MOFs Aided Sample Preparation (MASP) workflow that shrinks sample volume and integrates lysis, protein capture, protein digestion and peptide collection steps into a single PCR tube to minimize sample loss caused by non-specific absorption, is proposed further. MASP is validated to quantify ≈1800 proteins in 10 HEK-293T cells. MASP is applied to profile cerebrospinal fluid (CSF) proteome from cerebral stroke and brain damaged patients, and identified ≈3700 proteins in 1 µL CSF. MASP is further demonstrated to detect ≈9600 proteins in as few as 50 µg mouse brain tissues. MASP thus enables deep, scalable, and reproducible proteome on precious clinical samples with low abundant proteins.

Keywords: metal‐organic frameworks (MOFs); protein absorption; proteomics; trace samples.

MeSH terms

  • Animals
  • Boronic Acids* / chemistry
  • Brain / metabolism
  • HEK293 Cells
  • Humans
  • Lanthanoid Series Elements* / chemistry
  • Metal-Organic Frameworks* / chemistry
  • Mice
  • Proteome / analysis
  • Proteomics* / methods

Substances

  • Metal-Organic Frameworks
  • Boronic Acids
  • Lanthanoid Series Elements
  • Proteome