Mechanospray Ionization MS of Proteins Including in the Folded State and Polymers

Dugan, Liam; Bier, Mark E.

doi:10.1021/jasms.1c00344

Cited by 4 publications

(10 citation statements)

References 41 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, recent notable work demonstrating the use of alternative field-free ionization sources has shown the ability to produce high-quality spectra for native MS experiments. 88 The results presented here extend to such field-free approaches and suggest that they may offer the greatest ability to preserve structure for intractable species such as highly flexible proteins. This potential should serve as the impetus for developmental work to improve the overall sensitivity of field-free ionization sources.…”

Section: ■ Conclusionsupporting

confidence: 51%

“…For example, developing vibrating substrates that produce smaller droplets may dramatically improve the spectral quality. Indeed, recent notable work demonstrating the use of alternative field-free ionization sources has shown the ability to produce high-quality spectra for native MS experiments . The results presented here extend to such field-free approaches and suggest that they may offer the greatest ability to preserve structure for intractable species such as highly flexible proteins.…”

Section: Discussionmentioning

confidence: 52%

“…107 Notably, other field-free ionization sources have observed this behavior as well. 80,88 The CSDs of Ubiquitin have been further investigated in negative ion mode to see if similar results are obtained. As noted above, cESI is not stable in negative ion mode due to corona discharge.…”

Section: ■ Results and Discussionmentioning

confidence: 82%

“…These include (1) sonic spray, 79 (2) surface acoustic wave nebulization (SAWN), 80,81 (3) array of micromachined ultrasonic electrosprays (AMUSE), 82 (4) paper spray ionization, 83,84 (5) solvent assisted inlet ionization (SAII), 85,86 (6) vibrating tip, 87 and (7) mechanospray ionization (MoSI). 88 A new voltage-free ionization method was reported by Li and co-workers in 2018 termed vibrating sharp-edge spray ionization (VSSI). 89 The approach generates a droplet stream from a liquid substrate introduced directly to the sharp edge of a surface which is mechanically vibrated.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Over the years, a number of different spray-based ionization sources have been investigated for their ability to generate protein or peptide ions. These include (1) sonic spray, (2) surface acoustic wave nebulization (SAWN), , (3) array of micromachined ultrasonic electrosprays (AMUSE), (4) paper spray ionization, , (5) solvent assisted inlet ionization (SAII), , (6) vibrating tip, and (7) mechanospray ionization (MoSI) . A new voltage-free ionization method was reported by Li and co-workers in 2018 termed vibrating sharp-edge spray ionization (VSSI) .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Capillary Vibrating Sharp-Edge Spray Ionization Augments Field-Free Ionization Techniques to Promote Conformer Preservation in the Gas-Phase for Intractable Biomolecular Ions

et al. 2022

View full text Add to dashboard Cite

Field-free capillary vibrating sharp-edge spray ionization (cVSSI) is evaluated for its ability to conduct native mass spectrometry (MS) experiments. The charge state distributions for nine globular proteins are compared using field-free cVSSI, field-enabled cVSSI, and electrospray ionization (ESI). In general, for both positive and negative ion mode, the average charge state (q avg) increases for field-free cVSSI with increasing molecular weight similar to ESI. A clear difference is that the q avg is significantly lower for field-free conditions in both analyses. Two proteins, leptin and thioredoxin, exhibit bimodal charge state distributions (CSDs) upon the application of voltage in positive ion mode; only a monomodal distribution is observed for field-free conditions. In negative ion mode, thioredoxin exhibits a multimodal CSD upon the addition of voltage to cVSSI. Extensive molecular dynamics (MD) simulations of myoglobin and leptin in nanodroplets suggest that the multimodal CSD for leptin may originate from increased conformational “breathing” (decreased packing) and association with the droplet surface. These properties along with increased droplet charge appear to play critical roles in shifting ionization processes for some proteins. Further exploration and development of field-free cVSSI as a new ionization source for native MS especially as applied to more flexible biomolecular species is warranted.

show abstract

Section: ■ Conclusionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 52%

Section: ■ Results and Discussionmentioning

confidence: 82%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Capillary Vibrating Sharp-Edge Spray Ionization Augments Field-Free Ionization Techniques to Promote Conformer Preservation in the Gas-Phase for Intractable Biomolecular Ions

et al. 2022

View full text Add to dashboard Cite

show abstract

Portable mass spectrometry system: instrumentation, applications, and path to ‘omics analysis

et al. 2022

View full text Add to dashboard Cite

Mass spectrometry (MS) is an information rich analytical technique and plays a key role in various 'omics studies. Standard mass spectrometers are bulky and operate at high vacuum, which hinder their adoption by the broader community and utility in field applications. Developing portable mass spectrometers can significantly expand the application scope and user groups of MS analysis. This review discusses the basics and recent advancements in the development of key components of portable mass spectrometers including ionization source, mass analyzer, detector, and vacuum system. Further, major areas where portable mass spectrometers are applied are also discussed. Finally, a perspective on the further development of portable mass spectrometers including the potential benefits for 'omics analysis is provided.

show abstract

In‐droplet hydrogen–deuterium exchange to examine protein/peptide solution conformer heterogeneity

Sharif

Rahman

Mahmud

et al. 2023

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Rationale Many different structure analysis techniques are not capable of probing the heterogeneity of solution conformations. Here, we examine the ability of in‐droplet hydrogen–deuterium exchange (HDX) to directly probe solution conformer heterogeneity of a protein with mass spectrometry (MS) detection. Methods Two vibrating capillary vibrating sharp‐edge spray ionization (cVSSI) devices have been arranged such that they generate microdroplet plumes of the analyte and D2O reagent, which coalesce to form reaction droplets where HDX takes place in the solution environment. The native HDX–MS setup has been first explored for two model peptides that have distinct structural compositions in solution. The effectiveness of the multidevice cVSSI–HDX in illustrating structural details has been further exploited to investigate coexisting solution‐phase conformations of the protein ubiquitin. Results In‐droplet HDX reveals decreased backbone exchange for a model peptide that has a greater helix‐forming propensity. Differences in intrinsic rates of the alanine and serine residues may account for much of the observed protection. The data allow the first estimates of backbone exchange rates for peptides undergoing in‐droplet HDX. That said, the approach may hold greater potential for investigating the tertiary structure and structural transitions of proteins. For ubiquitin protein, HDX reactivity differences suggest that multiple conformers are present in native solutions. The addition of methanol to buffered aqueous solutions of ubiquitin results in increased populations of solution conformers of higher reactivity. Data analysis suggests that partially folded conformers such as the A‐state of ubiquitin increase with methanol content; the native state may be preserved to a limited degree even under stronger denaturation conditions. Conclusion The deuterium uptake after in‐droplet HDX has been observed to correspond to some degree with peptide backbone hydrogen protection based on differences in intrinsic rates of exchange. The presence of coexisting protein solution structures under native and denaturing solution conditions has been distinguished by the isotopic distributions of deuterated ubiquitin ions.

show abstract

Mechanospray Ionization MS of Proteins Including in the Folded State and Polymers

Cited by 4 publications

References 41 publications

Capillary Vibrating Sharp-Edge Spray Ionization Augments Field-Free Ionization Techniques to Promote Conformer Preservation in the Gas-Phase for Intractable Biomolecular Ions

Capillary Vibrating Sharp-Edge Spray Ionization Augments Field-Free Ionization Techniques to Promote Conformer Preservation in the Gas-Phase for Intractable Biomolecular Ions

Portable mass spectrometry system: instrumentation, applications, and path to ‘omics analysis

In‐droplet hydrogen–deuterium exchange to examine protein/peptide solution conformer heterogeneity

Contact Info

Product

Resources

About