Emergence of mass spectrometry detergents for membrane proteomics

Abstract

Detergents enable the investigation of membrane proteins by mass spectrometry. Detergent designers aim to improve underlying methodologies and are confronted with the challenge to design detergents with optimal solution and gas-phase properties. Herein, we review literature related to the optimization of detergent chemistry and handling and identify an emerging research direction: the optimization of mass spectrometry detergents for individual applications in mass spectrometry-based membrane proteomics. We provide an overview about qualitative design aspects including their relevance for the optimization of detergents in bottom-up proteomics, top-down proteomics, native mass spectrometry, and Nativeomics. In addition to established design aspects, such as charge, concentration, degradability, detergent removal, and detergent exchange, it becomes apparent that detergent heterogeneity is a promising key driver for innovation. We anticipate that rationalizing the role of detergent structures in membrane proteomics will serve as an enabling step for the analysis of challenging biological systems.

Keywords: Detergent; Mass spectrometry; Membrane; Omics; Protein.

Fig. 1

Mass spectrometry detergents for mass spectrometry–based membrane protein analysis. Schematic overview about detergent classes, e.g., non-ionic (blue), cationic (orange), or anionic (purple), a cell, and applications in life sciences that require detergents and aim for a better understanding of how a cell works (upper panel). Furthermore, a schematic overview about possible applications and related MS detergent classes involved in mass spectrometry–based membrane protein analysis is shown (lower panel)

Fig. 2

Mass spectrometry detergents for denaturing BUP and TDP experiments. Overview about detergent classes employed for denaturing BUP and TDP experiments, which are mainly anionic, cationic, and zwitter-ionic

Fig. 3

Mass spectrometry detergents for nMS and Nativeomics experiments. Overview about detergent classes employed for non-denaturing nMS and Nativeomics experiments. Related detergent classes are mainly non-ionic or zwitter-ionic

Fig. 4

Rationalizing the design of mass spectrometry detergents. Schematic showing an overview about qualitative design aspects for MS detergents and their relevance for individual steps in BUP, TDP, nMS, and Nativeomics. The optimal design of MS detergents depends on the application, e.g., denaturing BUP and TDP (left) or nMS and Nativeomics (right)