Physical Sciences and Mathematics Commons^™

Mechanism Of Thermal Protein Aggregation: Experiments And Molecular Dynamics Simulations On The High-Temperature Behavior Of Myoglobin., Yuen Ki Ng, Nastaran N Tajoddin, Pablo M Scrosati, Lars Konermann

Chemistry Publications

Proteins that encounter unfavorable solvent conditions are prone to aggregation, a phenomenon that remains poorly understood. This work focuses on myoglobin (Mb) as a model protein. Upon heating, Mb produces amorphous aggregates. Thermal unfolding experiments at low concentration (where aggregation is negligible), along with centrifugation assays, imply that Mb aggregation proceeds via globally unfolded conformers. This contrasts studies on other proteins that emphasized the role of partially folded structures as aggregate precursors. Molecular dynamics (MD) simulations were performed to gain insights into the mechanism by which heat-unfolded Mb molecules associate with one another. A prerequisite for these simulations was the …

Metal Release From A Biomedical Cocrmo Alloy In Mixed Protein Solutions Under Static And Sliding Conditions: Effects Of Protein Aggregation And Metal Precipitation, Zheng Wei, Valentine Romanovski, Luimar Filho, Cecilia Persson, Yolanda S. Hedberg

Chemistry Publications

Biomedical materials made of cobalt-chromium-molybdenum (CoCrMo) alloys are commonly used in artificial prostheses and dental implants, which are exposed to friction and load. The release of Co, Cr, and Mo from these surfaces is governed by physical and chemical processes. The extent of measured metal release from biomedical CoCrMo alloys into mixed protein solutions may be influenced by protein aggregation and metal precipitation effects. Metal release from, and the surface composition of, a CoCrMo alloy was investigated in physiological relevant solutions (phosphate buffered saline, PBS, with varying concentrations of fibrinogen from bovine plasma and/or bovine serum albumin) at pH 7.3 …

Characterization Of Ovarian Cancer-Derived Extracellular Vesicles By Surface-Enhanced Raman Spectroscopy., Nina M. Culum, Tyler T. Cooper, Gilles A. Lajoie, Thamara Dayarathna, Stephen H. Pasternak, Jiahui Liu, Yangxin Fu, Francois Lagugne-Labarthet, Lynne Marie Postovit

Chemistry Publications

Ovarian cancer is the most lethal gynecological malignancy, owing to the fact that most cases are diagnosed at a late stage. To improve prognosis and reduce mortality, we must develop methods for the early diagnosis of ovarian cancer. A step towards early and non-invasive cancer diagnosis is through the utilization of extracellular vesicles (EVs), which are nanoscale, membrane-bound vesicles that contain proteins and genetic material reflective of their parent cell. Thus, EVs secreted by cancer cells can be thought of as cancer biomarkers. In this paper, we present gold nanohole arrays for the capture of ovarian cancer (OvCa)-derived EVs and …

Polyglyoxylamides With A Ph-Mediated Solubility And Depolymerization Switch, Quinton E. A. Sirianni, Xiaoli Liang, Georgina K. Such, Elizabeth Gillies

Chemistry Publications

Self-immolative polymers (SIPs) are characterized by their ability to depolymerize in response to the cleavage of a single end-cap or backbone moiety, making them attractive for numerous applications including sensors, transient plastics, and delivery vehicles. For many applications, it would be desirable to have an SIP capable of depolymerizing selectively under mildly acidic aqueous conditions. However, the poor solubility of most SIPs in water, accompanied by the competing effects of end-cap cleavage and depolymerization mechanisms, has made this a challenge. Here, we describe the development of polyglyoxylamides (PGAms) with pendent amino groups to achieve solubility switching at mildly acidic pH, …

Using Covalent Modifications To Distinguish Protein Electrospray Mechanisms: Charged Residue Model (Crm) Vs. Chain Ejection Model (Cem), Lars Konermann, Douglas J. D. Pimlott

Chemistry Publications

Different mechanisms have been proposed for the formation of gaseous protein ions during electrospray ionization (ESI). In the charged residue model (CRM) ions are produced upon nanodroplet evaporation to dryness. This mechanism is thought to dominate in native ESI, where proteins retain compact conformations, with charge states close to the Rayleigh charge of protein-sized aqueous droplets. Much higher charge states are generated from proteins that are unfolded in solution. The chain ejection model (CEM) has been proposed for ESI under such denaturing conditions. In the CEM proteins are gradually expelled, while mobile H⁺ equilibrate between the droplet and its …

Hydrogen/Deuterium Exchange Measurements May Provide An Incomplete View Of Protein Dynamics: A Case Study On Cytochrome, Pablo M Scrosati, Victor Yin, Lars Konermann

Chemistry Publications

Many aspects of protein function rely on conformational fluctuations. Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) provides a window into these dynamics. Despite the widespread use of HDX-MS, it remains unclear whether this technique provides a truly comprehensive view of protein dynamics. HDX is mediated by H-bond-opening/closing events, implying that HDX methods provide an H-bond-centric view. This raises the question if there could be fluctuations that leave the H-bond network unaffected, thereby rendering them undetectable by HDX-MS. We explore this issue in experiments on cytochrome

Post-Polymerization ‘Click’ End-Capping Of Polyglyoxylate Self-Immolative Polymers, Peter G. Maschmeyer, Xiaoli Liang, Allison Hung, Oksana Ahmadzai, Annmaree L. Kenny, Yuan C. Luong, Timothy N. Forder, Haoxiang Zeng, Elizabeth R. Gillies, Derrick A. Roberts

Chemistry Publications

No abstract provided.

Self-Immolative Dendron Hydrogels, Karanpreet Gill, Xueli Mei, Elizabeth Gillies

Chemistry Publications

Smart hydrogels are of great interest in areas such as drug delivery and sensing. Dendrimer-based hydrogels can exhibit tunable properties due to their structural precision. We prepared hydrogels from self-immolative dendrons. Controlled hydrogel degradation in response to light was demonstrated and the hydrogel properties as a function of dendron generation were compared.

Atomistic Insights Into The Formation Of Nonspecific Protein Complexes During Electrospray Ionization., Elnaz Aliyari, Lars Konermann

Chemistry Publications

Native electrospray ionization (ESI)-mass spectrometry (MS) is widely used for the detection and characterization of multi-protein complexes. A well-known problem with this approach is the possible occurrence of nonspecific protein clustering in the ESI plume. This effect can distort the results of binding affinity measurements, and it can even generate gas-phase complexes from proteins that are strictly monomeric in bulk solution. By combining experiments and molecular dynamics (MD) simulations, the current work for the first time provides detailed insights into the ESI clustering of proteins. Using ubiquitin as a model system, we demonstrate how the entrapment of more than one …

Pressure-Induced Polymorphic Transformations Of Ethylenediamine Bisborane, Rongfeng Guan, Pan Wang, Yang Song, Viktor N. Staroverov

Chemistry Publications

Pressure-induced phase transitions of crystalline ethylenediamine bisborane (EDAB), a prospective hydrogen storage material, are investigated using vibrational spectroscopy, X-ray diffraction, evolutionary crystal structure prediction, and density functional theory. The results indicate that EDAB undergoes two transitions in the 0–17 GPa pressure range: the first one is near 1 GPa, from the orthorhombic ambient-pressure Pbca structure (phase I) to a monoclinic structure of P21/c symmetry (phase II); the second is near 7 GPa, from phase II to another P21/c structure (phase III). The latter coexists with phase II and remains the most stable form of EDAB up …

Bioaccessibility And Reactivity Of Alloy Powders Used In Powder Bed Fusion Additive Manufacturing, Yolanda S. Hedberg

Chemistry Publications

Exposure to metal particles via the inhalation route unavoidably takes place at occupational settings during additive manufacturing of metals and alloys. This calls for investigations on possible adverse health effects. This study focuses on virgin and reused powders of three iron- and nickel-based alloy powders (316L, IN718, 18Ni300) widely used in additive manufacturing, and dust powder of 18Ni300 generated during laser melting. Investigations were performed from a physico-chemical and toxicological perspective assessing their bioaccessibility in artificial lysosomal fluid (ALF, simulating lung exposure to respirable particles), corrosion behavior, surface morphology and composition, microstructure, hydrodynamic size distribution in ALF, and in-vitro toxicity …

Systematic And Collaborative Approach To Problem Solving Using X-Ray Photoelectron Spectroscopy, Neal Fairley, Vincent Fernandez, Mireille Richard-Plouet, Catherine Guillot-Deudon, John Walton, Emily Smith, Delphine Flahaut, Mark Greiner, Mark Biesinger, Sven Tougaard, David Morgan, Jonas Baltrusaitis

Chemistry Publications

The methodology presented within this work is a result of years of interactions between many junior and senior X-ray Photoelectron Spectroscopy (XPS) users operating within the CasaXPS spectral processing and interpretation program framework. In particular, discussions arising from a series of workshops have been a significant source for developing the overall XPS data processing concept and are the motivation for creating this work. These workshops organized by the Institut des Matériaux Jean Rouxel (IMN), Nantes gather both experienced and novice users of XPS for a week of discourse in conceptual experiment design and the resulting data processing. However, the framework …

Skin Permeation Of Nickel, Cobalt And Chromium Salts In Ex Vivo Human Skin, Visualized Using Mass Spectrometry Imaging, Lina Hagvall, Masoumeh Dowlatshahi Pour, Jiabao Feng, Moshtak Karma, Yolanda Hedberg, Per Malmberg

Chemistry Publications

Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previ-ously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration …

Genotoxicity And Inflammatory Potential Of Stainless Steel Welding Fume Particles: An In Vitro Study On Standard Vs Cr(Vi)-Reduced Flux-Cored Wires And The Role Of Released Metals., Sarah Mccarrick, Valentin Romanovski, Zheng Wei, Elin M Westin, Kjell-Arne Persson, Klara Trydell, Richard Wagner, Inger Odnevall, Yolanda S Hedberg, Hanna L Karlsson

Chemistry Publications

Welders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA …

Extending Nanoscale Patterning With Multipolar Surface Plasmon Resonances., Issam Kherbouche, Danielle Macrae, Théo Geronimi Jourdain, François Lagugné-Labarthet, Azedine Lamouri, Alexandre Chevillot Biraud, Claire Mangeney, Nordin Félidj

Chemistry Publications

Plasmonic excitation of metallic nanoparticles can trigger chemical reactions at the nanoscale. Such optical effects can also be employed to selectively and locally graft photopolymer layers at the nanostructure surface, and, when combined with a surface functionalization agent, new pathways can be explored to modify the surface of a plasmonic nanoparticle. Among these approaches, diazonium salt chemistry is seen as an attractive strategy due to the high photoinduced reactivity of these salts. In this work, we demonstrate that it is possible to trigger the site-selective grafting of aryl films derived from diazonium salts on distinct nano-localized area of single gold …

Characterization Of Extracellular Vesicles Derived From Mesenchymal Stromal Cells By Surface-Enhanced Raman Spectroscopy., Nina M Ćulum, Tyler T Cooper, Gillian I Bell, David A Hess, François Lagugné-Labarthet

Chemistry Publications

Extracellular vesicles (EVs) are secreted by all cells into bodily fluids and play an important role in intercellular communication through the transfer of proteins and RNA. There is evidence that EVs specifically released from mesenchymal stromal cells (MSCs) are potent cell-free regenerative agents. However, for MSC EVs to be used in therapeutic practices, there must be a standardized and reproducible method for their characterization. The detection and characterization of EVs are a challenge due to their nanoscale size as well as their molecular heterogeneity. To address this challenge, we have fabricated gold nanohole arrays of varying sizes and shapes by …

Characterization Of Extracellular Vesicles Derived From Mesenchymal Stromal Cells By Surface-Enhanced Raman Spectroscopy., Nina M Ćulum, Tyler T Cooper, Gillian I Bell, David A Hess, François Lagugné-Labarthet

Chemistry Publications

Extracellular vesicles (EVs) are secreted by all cells into bodily fluids and play an important role in intercellular communication through the transfer of proteins and RNA. There is evidence that EVs specifically released from mesenchymal stromal cells (MSCs) are potent cell-free regenerative agents. However, for MSC EVs to be used in therapeutic practices, there must be a standardized and reproducible method for their characterization. The detection and characterization of EVs are a challenge due to their nanoscale size as well as their molecular heterogeneity. To address this challenge, we have fabricated gold nanohole arrays of varying sizes and shapes by …

Characterization Of Extracellular Vesicles Derived From Mesenchymal Stromal Cells By Surface-Enhanced Raman Spectroscopy., Nina M. Culum, Tyler T. Cooper, Gillian I. Bell, David A. Hess, François Lagugné-Labarthet

Chemistry Publications

Extracellular vesicles (EVs) are secreted by all cells into bodily fluids and play an important role in intercellular communication through the transfer of proteins and RNA. There is evidence that EVs specifically released from mesenchymal stromal cells (MSCs) are potent cell-free regenerative agents. However, for MSC EVs to be used in therapeutic practices, there must be a standardized and reproducible method for their characterization. The detection and characterization of EVs are a challenge due to their nanoscale size as well as their molecular heterogeneity. To address this challenge, we have fabricated gold nanohole arrays of varying sizes and shapes by …

Exploiting Light Interferences To Generate Micrometer-High Superstructures From Monomeric Azo Materials With Extensive Orientational Mobility, Florent Rodriguez, Joachim Jelken, Nicolas Delpouve, Adèle Laurent, Bertrand Garnier, Jean-Luc Duvail, Francois Lagugne-Labarthet, Eléna Ishow

Chemistry Publications

Photochromic azo materials have stirred considerable interest for their ability to mechanically respond to polarized light through large photo-induced migration and orientation processes. In order to apprehend the microscopic dynamics behind the extensive mass transport occurring under interferential illumination, two azo compounds differing by their propen-sity to form hydrogen bonds are synthesized and processed as nondoped glassy thin films. Interferential irradiation using polarization and intensity patterns reveals fully distinct responses. Regular nanometer-high surface relief gratings transform into micrometer superstructures with an ampli-tude ten times higher than the initial film thickness when using the latter polarization. Systematic comparisons between the azo …

Analytical Survey Of Tattoo Inks—A Chemical And Legal Perspective With Focus On Sensitizing Substances, Xuying Wang, Leila Josefsson, Silvia Meschnark, Marie-Louise Lind, Åsa Emmer, Walter Goessler, Yolanda S. Hedberg

Chemistry Publications

Background

Tattoo inks have been reported to elicit allergic contact dermatitis.

Objectives

To investigate the labels and the contents of metals and pigments in tattoo inks, considering restrictions within the European Union.

Methods

Seventy-three tattoo inks currently available on the market, either bought or donated (already used), were investigated for trace metals and pigments by inductively coupled plasma mass spectrometry and by matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry.

Results

Ninety-three percent of the bought tattoo inks violated European, legal requirements on labeling. Fifty percent of the tattoo inks declared at least one pigment ingredient incorrectly. Sixty-one percent …

Effects Of Amino Acid Side-Chain Length And Chemical Structure On Anionic Polyglutamic And Polyaspartic Acid Cellulose-Based Polyelectrolyte Brushes., Dmitry Tolmachev, George Mamistvalov, Natalia Lukasheva, Sergey Larin, Mikko Karttunen

Chemistry Publications

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α,L-glutamic acid and α,L-aspartic acid grafted on cellulose in the presence of divalent CaCl₂ salt at different concentrations. The motivation is to search for ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side-chain length, the chemical structure and their interplay are required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the …

Keap1 Cancer Mutants: A Large-Scale Molecular Dynamics Study Of Protein Stability., Carter J Wilson, Megan Chang, Mikko Karttunen, Wing-Yiu Choy

Chemistry Publications

We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise …

Using Chemical Speciation Modelling To Discuss Variations In Patch Test Reactions To Different Aluminium And Chromium Salts, Saman Nikpour, Yolanda S. Hedberg

Chemistry Publications

Background: Allergic contact dermatitis to metals is diagnosed by applying a metal salt in a patch test. The bioavailability of the metal salt might depend on the choice of metal salt, the concentration, sweat composition, and pH.

Objectives: The main purpose of this study was to apply chemical speciation modelling, which is based on experimentally derived input data and calculates the concentrations of chemical forms (species) in solutions, to reproduce and discuss clinical patch test results of aluminium and chromium.

Methods: Joint Expert Speciation System (JESS), Hydra/Medusa, and Visual Minteq were employed to study the bioavailable fraction and chemical form …

Patch Testing With Aluminium Finn Chambers Could Give False-Positive Reactions In Patients With Contact Allergy To Aluminium, Lisbeth Rosholm Comstedt, Jakob Dahlin, Magnus Bruze, Yolanda S. Hedberg, Mihály Matura, Cecilia Svedman

Chemistry Publications

Background

Earlier laboratory studies have shown that sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride trigger the release of aluminium (Al) from Finn Chambers (FC).

Objectives

To investigate whether aluminium realease from FC could influence the diagnostic outcome of patch testing with FC.

Method

A retrospective analysis of patch test results from 2010 to 2019 was performed. A two-sided Fisher's exact test was used to calculate any overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride.

Results

A total of 5446 patients had been tested …

Mobile Protons Limit The Stability Of Salt Bridges In The Gas Phase: Implications For The Structures Of Electrosprayed Protein Ions., Lars Konermann, Elnaz Aliyari, Justin H Lee

Chemistry Publications

Electrosprayed protein ions can retain native-like conformations. The intramolecular contacts that stabilize these compact gas-phase structures remain poorly understood. Recent work has uncovered abundant salt bridges in electrosprayed proteins. Salt bridges are zwitterionic BH⁺/A^- contacts. The low dielectric constant in the vacuum strengthens electrostatic interactions, suggesting that salt bridges could be a key contributor to the retention of compact protein structures. A problem with this assertion is that H⁺ are mobile, such that H⁺ transfer can convert salt bridges into neutral B⁰/HA⁰ contacts. This possible salt bridge annihilation puts into question the …

A Divergent Strategy For The Synthesis Of Redox-Active Verdazyl Radical Polymers, Francois Magnan, Jasveer S. Dhindsa, Michael Anghel, Paul Bazylweski, Giovanni Fanchini, Joe Gilroy

Chemistry Publications

Stable radical polymers have attracted significant attention due to their use as magnetic materials, (co)catalysts in organic synthesis, and as functional components of organic electronics including batteries and memory devices. Despite their importance, a relatively narrow range of synthetic strategies exist for their production. The most common examples involve the transition-metal catalyzed polymerization of radical-containing monomers or the sequential polymerization of monomers containing radical precursors and their post-polymerization conversion to radicals. Post-polymerization installation of stable radicals is not commonly reported. Copper-assisted azide-alkyne cycloaddition (CuAAC) chemistry has seen limited use in this regard, but only for the production of p-conjugated and …

Polyesters Based On Aspartic Acid And Poly(Ethylene Glycol): Functional Polymers For Hydrogel Preparation, Trent N. Gordon, Anna Kornmuller, Yashveer Soni, Lauren E. Flynn, Elizabeth R. Gillies

Chemistry Publications

Hydrogels are commonly used as scaffolds for the preparation of three-dimensional tissue constructs and for the encapsulation and delivery of cells in regenerative medicine. Polyesters are an attractive class of polymers for hydrogel preparation. However, most polyesters have hydrophobic backbones and lack pendent groups that can be chemically functionalized. We describe here the development of water-soluble polyesters based on aspartic acid and poly(ethylene glycol) (PEG) (600 or 1500 g/mol), having pendent reactive amines. The reactivity of these amines with methacrylic anhydride, maleic anhydride, and itaconic anhydride was explored for the introduction of crosslinkable groups. The resulting methacrylamide-functionalized polymers were successfully …

Polymer Particles For The Intra-Articular Delivery Of Drugs To Treat Osteoarthritis, Xueli Mei, Ian J. Villamagna, Tony Nguyen, Frank Beier, C. Thomas Appleton, Elizabeth R. Gillies

Chemistry Publications

Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, …

Detection Of Gold Cysteine Thiolate Complexes On Gold Nanoparticles With Time-Of-Flight Secondary Ion Mass Spectrometry, Yolanda Hedberg, Jonas Hedberg, Valentin Romanovski, Elena Romanovskaia, Heng-Yong Nie

Chemistry Publications

Gold (Au) nanoparticles (NPs) are widely used in nanomedical applications as a carrier for molecules designed for different functionalities. Previous findings suggested that biological molecules, including amino acids, could contribute to the dissolution of Au NPs in physiological environments and that this phenomenon was size-dependent. We, therefore, investigated the interactions of L-cysteine with 5-nm Au NPs by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS). This was achieved by loading Au NPs on a clean aluminum (Al) foil and immersing it in an aqueous solution containing L-cysteine. Upon rinsing off the excessive cysteine molecules, ToF-SIMS confirmed the formation of gold …

Ph-Sensitive Chitosan Nanoparticles For Salivary Protein Delivery, Yi Zhu, Lina M. Marin, Yizhi Xiao, Elizabeth R. Gillies, Walter L. Siqueira

Chemistry Publications

Salivary proteins such as histatins (HTNs) have demonstrated critical biological functions directly related to tooth homeostasis and prevention of dental caries. However, HTNs are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparti-cles (CNs) have been proposed as potential carriers to protect proteins from enzymatic degradation at physiological salivary pH. Four different types of chitosan polymers were investigated and the optimal formulation had good batch to batch reproducibility, with an average hydrodynamic diame-ter of 144 ± 6 nm, a polydispersity index of 0.15 ± 0.04, and a zeta potential of 18 ± 4 mV at …