Surfactant-assisted one-pot sample preparation for label-free single-cell proteomics

Chia Feng Tsai, Pengfei Zhang, David Scholten, Kendall Martin, Yi Ting Wang, Rui Zhao, William B. Chrisler, Dhwani B. Patel, Maowei Dou, Yuzhi Jia, Carolina Reduzzi, Xia Liu, Ronald J. Moore, Kristin E. Burnum-Johnson, Miao Hsia Lin, Chuan Chih Hsu, Jon M. Jacobs, Jacob Kagan, Sudhir Srivastava, Karin D. RodlandH. Steven Wiley, Wei Jun Qian, Richard D. Smith, Ying Zhu, Massimo Cristofanilli, Tao Liu, Huiping Liu, Tujin Shi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for 'all-in-one' one-pot sample preparation. This 'all-in-one' method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.

Original languageEnglish (US)
Pages (from-to)265
Number of pages1
JournalCommunications Biology
Volume4
Issue number1
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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