Mass Spectrometry Imaging of Lipids in Human Skin Disease Model Hidradenitis Suppurativa by Laser Desorption Ionization from Silicon Nanopost Arrays

Jarod A Fincher,Paola Parlanti,Christine A Brantner,Jacqueline E Dyer,Derek R Jones,Victoria K Shanmugam,Andrew R Korte,Russell K Pirlo,Nicholas J Morris,Anastas Popratiloff,Akos Vertes

doi:10.1038/s41598-019-53938-0

Jarod A Fincher, Paola Parlanti + Show 9 more

Open Access

https://doi.org/10.1038/s41598-019-53938-0

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Abstract

Neutral lipids have been implicated in a host of potentially debilitating human diseases, such as heart disease, type-2 diabetes, and metabolic syndrome. Matrix-assisted laser desorption ionization (MALDI), the method-of-choice for mass spectrometry imaging (MSI), has led to remarkable success in imaging several lipid classes from biological tissue sections. However, due to ion suppression by phospholipids, MALDI has limited ability to efficiently ionize and image neutral lipids, such as triglycerides (TGs). To help overcome this obstacle, we have utilized silicon nanopost arrays (NAPA), a matrix-free laser desorption ionization (LDI) platform. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease of the apocrine sweat glands. The ability of NAPA to efficiently ionize lipids is exploited in the analysis of human skin samples from sufferers of HS. Ionization by LDI from NAPA allows for the detection and imaging of a number of neutral lipid species, including TGs comprised of shorter, odd-chain fatty acids, which strongly suggests an increased bacterial load within the host tissue, as well as hexosylceramides (HexCers) and galabiosyl-/lactosylceramides that appear to be correlated with the presence of HS. Our results demonstrate that NAPA-LDI-MSI is capable of imaging and potentially differentiating healthy and diseased human skin tissues based on changes in detected neutral lipid composition.

Highlights

Www.nature.com/scientificreports first mass spectrometry imaging (MSI) platforms to capture the distributions of diverse chemical species in biological tissues[13,14]
To account for natural variation of lipid distributions within tissue sections, comparisons between control and Hidradenitis suppurativa tissues were constrained to two distinct regions identified by tissue morphology and confirmed by subsequently identified biomarkers
Principal component analysis (PCA) of spectra obtained from the follicle/apocrine sweat gland region of control and Hidradenitis suppurativa (HS) skin sections allowed for the distinction of the two sample types

Summary

Introduction

Www.nature.com/scientificreports first MSI platforms to capture the distributions of diverse chemical species in biological tissues[13,14]. Several novel methods, incorporating metal nanoparticles in place of organic matrices, have been developed facilitating the detection and imaging of TGs in the presence of PCs22–24 While these modifications have helped to extend the attainable lipid coverage in MALDI-MSI experiments, they still require deposition of a UV-absorbing material onto the tissue for MSI. Since the emergence of MALDI-MSI, several innovative matrix-free MSI platforms such as nanostructure-initiator mass spectrometry (NIMS), desorption/ionization on silicon (DIOS), desorption electrospray ionization (DESI), and laser ablation electrospray ionization (LAESI) have been developed These techniques were developed for or adapted to imaging with the goals of circumventing the low mass interference introduced by the MALDI matrix, minimizing sample preparation, and extending the attainable molecular coverage for MSI applications[28,29,30,31,32,33,34,35,36]. To illustrate potential medical applications, we apply NAPA-LDI-MSI to study lipid profiles and localizations in skin samples obtained from patients diagnosed with Hidradenitis suppurativa (HS), a chronic skin disease that causes inflammation and seriously compromises quality of life for many sufferers

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