Top-Down Mass Spectrometry Imaging of Intact Proteins by LAESI FT-ICR MS

TL;DR

This paper demonstrates top-down mass spectrometry imaging of intact proteins directly from tissue surfaces using LAESI combined with FT-ICR MS, enabling protein identification without sample pre-treatment.

Contribution

It introduces a novel method combining LAESI with FT-ICR MS for top-down proteomics imaging of intact proteins from biological tissues.

Findings

Successful imaging of intact proteins from tissue sections.

Identification of hemoglobin α chain directly from tissue.

Validation of LAESI FT-ICR for top-down proteomics.

Abstract

Laser Ablation Electrospray Ionization is a recent development in mass spectrometry imaging. It has been shown that lipids and small metabolites can be imaged in various samples such as plant material, tissue sections or bacterial colonies without anysample pre-treatment. Further, laser ablation electrospray ionization has been shown to produce multiply charged protein ions from liquids or solid surfaces. This presents a means to address one of the biggest challenges in mass spectrometry imaging; the identification of proteins directly from biological tissue surfaces. Such identification is hindered by the lack of multiply charged proteins in common MALDI ion sources and the difficulty of performing tandem MS on such large, singly charged ions. We present here top-down identification of intact proteins from tissue with a LAESI ion source combined with a hybrid ion-trap FT-ICR mass spectrometer. The performance of the system was first tested with a standard protein with ECD and IRMPD fragmentation to prove the viability of LAESI FT-ICR for top-down proteomics. Finally, the imaging of a tissue section was performed, where a number of intact proteins were measured and the hemoglobin {\alpha} chain was identified directly from tissue using collision-induced dissociation and infrared multiphoton dissociation fragmentation.