New Mass-Spectrometry-Compatible Degradable Surfactant for Tissue Proteomics

Tissue
proteomics is increasingly recognized for its role in biomarker
discovery and disease mechanism investigation. However, protein solubility
remains a significant challenge in mass spectrometry (MS)-based tissue
proteomics. Conventional surfactants such as sodium dodecyl sulfate
(SDS), the preferred surfactant for protein solubilization, are not
compatible with MS. Herein, we have screened a library of surfactant-like
compounds and discovered an MS-compatible degradable surfactant (MaSDeS)
for tissue proteomics that solubilizes all categories of proteins
with performance comparable to SDS. The use of MaSDeS in the tissue
extraction significantly improves the total number of protein identifications
from commonly used tissues, including tissue from the heart, liver,
and lung. Notably, MaSDeS significantly enriches membrane proteins,
which are often under-represented in proteomics studies. The acid
degradable nature of MaSDeS makes it amenable for high-throughput
MS-based
proteomics. In addition, the thermostability of MaSDeS allows for
its use in experiments requiring high temperature to facilitate protein
extraction and solubilization. Furthermore, we have shown that MaSDeS
outperforms the other MS-compatible surfactants in terms of overall
protein solubility and the total number of identified proteins in
tissue proteomics. Thus, the use of MaSDeS will greatly advance tissue
proteomics and realize its potential in basic biomedical and clinical
research. MaSDeS could be utilized in a variety of proteomics studies
as well as general biochemical and biological experiments that employ
surfactants for protein solubilization.

组织蛋白质组学（tissue proteomics）在生物标志物发现与疾病机制研究中的作用日益受到认可。然而，在基于质谱（mass spectrometry, MS）的组织蛋白质组学研究中，蛋白质溶解度仍是一项重大挑战。常规表面活性剂如十二烷基硫酸钠（sodium dodecyl sulfate, SDS）——作为蛋白质增溶的首选表面活性剂——却无法与质谱兼容。本研究筛选了类表面活性剂化合物库，开发出一种可与质谱兼容的可降解表面活性剂（MaSDeS）用于组织蛋白质组学研究，该试剂可溶解所有类别蛋白质，性能与SDS相当。将MaSDeS应用于组织提取流程，可显著提升心脏、肝脏、肺等常用组织样本的蛋白质鉴定总数。尤为关键的是，MaSDeS可显著富集蛋白质组学研究中通常占比偏低的膜蛋白。MaSDeS的酸降解特性使其可适配高通量基于质谱的蛋白质组学研究。此外，MaSDeS具备热稳定性，可用于需通过高温促进蛋白质提取与增溶的实验。进一步研究表明，在整体蛋白质溶解度与组织蛋白质组学的蛋白质鉴定总数方面，MaSDeS均优于其他与质谱兼容的表面活性剂。因此，采用MaSDeS将极大推动组织蛋白质组学研究的发展，充分释放其在基础生物医学与临床研究中的应用潜力。MaSDeS不仅可应用于各类蛋白质组学研究，还可用于以表面活性剂实现蛋白质增溶的通用生化与生物学实验。