Abstract

(Bio-)nanoparticle analysis employing a nano-electrospray gas-phase electrophoretic mobility molecular analyzer (native nES GEMMA) also known as nES differential mobility analyzer (nES DMA) is based on surface-dry analyte separation at ambient pressure. Based on electrophoretic principles, single-charged nanoparticles are separated according to their electrophoretic mobility diameter (EMD) corresponding to the particle size for spherical analytes. Subsequently, it is possible to correlate the (bio-)nanoparticle EMDs to their molecular weight (MW) yielding a corresponding fitted curve for an investigated analyte class. Based on such a correlation, (bio-)nanoparticle MW determination via its EMD within one analyte class is possible. Turning our attention to icosahedral, non-enveloped virus-like particles (VLPs), proteinaceous shells, we set up an EMD/MW correlation. We employed native electrospray ionization mass spectrometry (native ESI MS) to obtain MW values of investigated analytes, where possible, after extensive purification. We experienced difficulties in native ESI MS with time-of-flight (ToF) detection to determine MW due to sample inherent characteristics, which was not the case for charge detection (CDMS). nES GEMMA exceeds CDMS in speed of analysis and is likewise less dependent on sample purity and homogeneity. Hence, gas-phase electrophoresis yields calculated MW values in good approximation even when charge resolution was not obtained in native ESI ToF MS. Therefore, both methods-native nES GEMMA-based MW determination via an analyte class inherent EMD/MW correlation and native ESI MS-in the end relate (bio-)nanoparticle MW values. However, they differ significantly in, e.g., ease of instrument operation, sample and analyte handling, or costs of instrumentation.Graphical abstract

Highlights

  • Viruses are nanoparticles of biological origin: A proteinaceous capsid protects the viral genome from the exterior

  • It was the aim of our investigation to analyze virus-like particles (VLPs) material with gas-phase electrophoresis on a native nES GEMMA instrument and to compare results with data obtained from native ESI MS and from literature

  • Native nES GEMMA analysis of VLPs In previous work, we had already described the analysis of VLP or VLP-like material based on hepatitis B virus capsids (HBV) with two icosahedral symmetries [12] and subviral particles of a human rhinovirus serotype (HRV-A2) [4]

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Summary

Introduction

Viruses are nanoparticles of biological origin: A proteinaceous capsid protects the viral genome from the exterior. Additional protection can be conveyed by a lipid membrane, which is modified by (glyco-) proteins to enable attachment to target cells (e.g., [1]). Upon target cell infection, the genomic material of the virus is intended for release. This concept is of interest for pharmacological applications as virus bionanoparticles can be interpreted as carriers enabling the shielded, targeted transport of cargo material. Viral particles without any encapsulated cargo can be employed for vaccination. In both cases, corresponding particles are referred to as virus-like particles (VLPs) (e.g., [2])

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