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19 pages, 11603 KiB

Open AccessArticle

Aggregation of an Amyloidogenic Peptide on Gold Surfaces

by David L. Cheung

Biomolecules 2023, 13(8), 1261; https://doi.org/10.3390/biom13081261 - 18 Aug 2023

Viewed by 1043

Abstract

Solid surfaces have been shown to affect the aggregation and assembly of many biomolecular systems. One important example is the formation of protein fibrils, which can occur on a range of biological and synthetic surfaces. The rate of fibrillation depends on both the [...] Read more.

Solid surfaces have been shown to affect the aggregation and assembly of many biomolecular systems. One important example is the formation of protein fibrils, which can occur on a range of biological and synthetic surfaces. The rate of fibrillation depends on both the protein structure and the surface chemistry, with the different molecular and oligomer structures adopted by proteins on surfaces likely to be crucial. In this paper, the aggregation of the model amyloidogenic peptide, A

β

(16–22), corresponding to a hydrophobic segment of the amyloid beta protein on a gold surface is studied using molecular dynamics simulation. Previous simulations of this peptide on gold surfaces have shown that it adopts conformations on surfaces that are quite different from those in bulk solution. These simulations show that this then leads to significant differences in the oligomer structures formed in solution and on gold surfaces. In particular, oligomers formed on the surface are low in beta-strands so are unlike the structures formed in bulk solution. When oligomers formed in solution adsorb onto gold surfaces they can then restructure themselves. This can then help explain the inhibition of A

β

(16–22) fibrillation by gold surfaces and nanoparticles seen experimentally. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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21 pages, 3365 KiB

Open AccessEditor’s ChoiceArticle

Hemocompatibility of β-Cyclodextrin-Modified (Methacryloyloxy)ethyl Phosphorylcholine Coated Magnetic Nanoparticles

by Shuhui Li, Mehdi Ghaffari Sharaf, Elyn M. Rowe, Katherine Serrano, Dana V. Devine and Larry D. Unsworth

Biomolecules 2023, 13(8), 1165; https://doi.org/10.3390/biom13081165 - 25 Jul 2023

Viewed by 1199

Abstract

Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that [...] Read more.

Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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17 pages, 3567 KiB

Open AccessEditor’s ChoiceArticle

Goldilocks Dilemma: LPS Works Both as the Initial Target and a Barrier for the Antimicrobial Action of Cationic AMPs on E. coli

by Martin Jakubec, Fredrik G. Rylandsholm, Philip Rainsford, Mitchell Silk, Maxim Bril’kov, Tone Kristoffersen, Eric Juskewitz, Johanna U. Ericson and John Sigurd M. Svendsen

Biomolecules 2023, 13(7), 1155; https://doi.org/10.3390/biom13071155 - 20 Jul 2023

Cited by 5 | Viewed by 1785

Abstract

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs [...] Read more.

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane. A combination of SPR and NMR experiments provide evidence suggesting that cationic AMPs first bind to the negatively charged LPS before reaching a binding place in the lipid bilayer. In the event that the initial LPS-binding is too strong (corresponding to a low dissociation rate), the cationic AMPs cannot effectively get from the LPS to the membrane, and their antimicrobial potency will thus be diminished. On the other hand, the AMPs must also be able to effectively interact with the membrane to exert its activity. The ability of the studied cyclic hexapeptides to bind LPS and to translocate into a lipid membrane is related to the nature of the cationic charge (arginine vs. lysine) and to the distribution of hydrophobicity along the molecule (alternating vs. clumped tryptophan). Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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17 pages, 2983 KiB

Open AccessArticle

Cellular Response to Bone Morphogenetic Proteins-2 and -7 Covalently Bound to Photocrosslinked Heparin–Diazoresin Multilayer

by Magdalena Wytrwal, Małgorzata Sekuła-Stryjewska, Agata Pomorska, Ewa Oclon, Ewa Zuba-Surma, Szczepan Zapotoczny and Krzysztof Szczubiałka

Biomolecules 2023, 13(5), 842; https://doi.org/10.3390/biom13050842 - 15 May 2023

Cited by 2 | Viewed by 1404

Abstract

Despite the plethora of research that exists on recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and rhBMP-7) and has been clinically approved, there is still a need to gain information that would allow for their more rational use in bone implantology. The [...] Read more.

Despite the plethora of research that exists on recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and rhBMP-7) and has been clinically approved, there is still a need to gain information that would allow for their more rational use in bone implantology. The clinical application of supra-physiological dosages of these superactive molecules causes many serious adverse effects. At the cellular level, they play a role in osteogenesis and cellular adhesion, migration, and proliferation around the implant. Therefore, in this work, we investigated the role of the covalent binding of rhBMP-2 and rhBMP-7 separately and in combination with ultrathin multilayers composed of heparin and diazoresin in stem cells. In the first step, we optimized the protein deposition conditions via quartz crystal microbalance (QCM). Then, atomic force microscopy (AFM) and enzyme-linked immunosorbent assay (ELISA) were used to analyze protein–substrate interactions. The effect of the protein binding on the initial cell adhesion, migration, and short-term expression of osteogenesis markers was tested. In the presence of both proteins, cell flattening and adhesion became more prominent, resulting in limited motility. However, the early osteogenic marker expression significantly increased compared to the single protein systems. The presence of single proteins resulted in the elongation of cells, which promoted their migration activity. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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14 pages, 2076 KiB

Open AccessArticle

Rheology and Gelation of Hyaluronic Acid/Chitosan Coacervates

by A. Basak Kayitmazer, Fatih Comert, Henning H. Winter and Phillip B. Messersmith

Biomolecules 2022, 12(12), 1817; https://doi.org/10.3390/biom12121817 - 5 Dec 2022

Cited by 4 | Viewed by 2764

Abstract

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly [...] Read more.

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly on the molecular weight of the polymers. Moduli for coacervates were found significantly higher than those of individual HA and CHI physical gels. A remarkable 1.5-fold increase in moduli was noted when catechol-conjugated HA and CHI were used instead. This was attributed to the conversion of coacervates to chemical gels by oxidation of 3,4-dihydroxyphenylalanine (DOPA) groups in HA and CHI to di-DOPA crosslinks. These rheological results put HA/CHI coacervates in the category of strong candidates as injectable tissue scaffolds or medical adhesives. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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17 pages, 4115 KiB

Open AccessArticle

Mimicking Pseudo-Virion Interactions with Abiotic Surfaces: Deposition of Polymer Nanoparticles with Albumin Corona

by Małgorzata Nattich-Rak, Marta Sadowska, Maja Motyczyńska and Zbigniew Adamczyk

Biomolecules 2022, 12(11), 1658; https://doi.org/10.3390/biom12111658 - 8 Nov 2022

Cited by 2 | Viewed by 1448

Abstract

Adsorption of human serum albumin (HSA) molecules on negatively charged polystyrene microparticles was studied using the dynamic light scattering, the electrophoretic and the solution depletion methods involving atomic force microscopy. Initially, the physicochemical characteristics of the albumin comprising the hydrodynamic diameter, the zeta [...] Read more.

Adsorption of human serum albumin (HSA) molecules on negatively charged polystyrene microparticles was studied using the dynamic light scattering, the electrophoretic and the solution depletion methods involving atomic force microscopy. Initially, the physicochemical characteristics of the albumin comprising the hydrodynamic diameter, the zeta potential and the isoelectric point were determined as a function of pH. Analogous characteristics of the polymer particles were acquired, including their size and zeta potential. The formation of albumin corona on the particles was investigated in situ by electrophoretic mobility measurements. The size, stability and electrokinetic properties of the particles with the corona were also determined. The particle diameter was equal to 125 nm, which coincides with the size of the SARS-CoV-2 virion. The isoelectric point of the particles appeared at a pH of 5. The deposition kinetics of the particles was determined by atomic force microscopy (AFM) under diffusion and by quartz microbalance (QCM) under flow conditions. It was shown that the deposition rate at a gold sensor abruptly vanished with pH following the decrease in the zeta potential of the particles. It is postulated that the acquired results can be used as useful reference systems mimicking virus adsorption on abiotic surfaces. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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Review

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48 pages, 2961 KiB

Open AccessReview

Biocompatible Macroion/Growth Factor Assemblies for Medical Applications

by Aneta Michna, Agata Pomorska and Ozlem Ozcan

Biomolecules 2023, 13(4), 609; https://doi.org/10.3390/biom13040609 - 28 Mar 2023

Cited by 1 | Viewed by 1854

Abstract

Growth factors are a class of proteins that play a role in the proliferation (the increase in the number of cells resulting from cell division) and differentiation (when a cell undergoes changes in gene expression becoming a more specific type of cell) of [...] Read more.

Growth factors are a class of proteins that play a role in the proliferation (the increase in the number of cells resulting from cell division) and differentiation (when a cell undergoes changes in gene expression becoming a more specific type of cell) of cells. They can have both positive (accelerating the normal healing process) and negative effects (causing cancer) on disease progression and have potential applications in gene therapy and wound healing. However, their short half-life, low stability, and susceptibility to degradation by enzymes at body temperature make them easily degradable in vivo. To improve their effectiveness and stability, growth factors require carriers for delivery that protect them from heat, pH changes, and proteolysis. These carriers should also be able to deliver the growth factors to their intended destination. This review focuses on the current scientific literature concerning the physicochemical properties (such as biocompatibility, high affinity for binding growth factors, improved bioactivity and stability of the growth factors, protection from heat, pH changes or appropriate electric charge for growth factor attachment via electrostatic interactions) of macroions, growth factors, and macroion-growth factor assemblies, as well as their potential uses in medicine (e.g., diabetic wound healing, tissue regeneration, and cancer therapy). Specific attention is given to three types of growth factors: vascular endothelial growth factors, human fibroblast growth factors, and neurotrophins, as well as selected biocompatible synthetic macroions (obtained through standard polymerization techniques) and polysaccharides (natural macroions composed of repeating monomeric units of monosaccharides). Understanding the mechanisms by which growth factors bind to potential carriers could lead to more effective delivery methods for these proteins, which are of significant interest in the diagnosis and treatment of neurodegenerative and civilization diseases, as well as in the healing of chronic wounds. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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20 pages, 1791 KiB

Open AccessReview

Interfacial Peptides as Affinity Modulating Agents of Protein-Protein Interactions

by Pavel V. Ershov, Yuri V. Mezentsev and Alexis S. Ivanov

Biomolecules 2022, 12(1), 106; https://doi.org/10.3390/biom12010106 - 8 Jan 2022

Cited by 3 | Viewed by 3025

Abstract

The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate [...] Read more.

The identification of disease-related protein-protein interactions (PPIs) creates objective conditions for their pharmacological modulation. The contact area (interfaces) of the vast majority of PPIs has some features, such as geometrical and biochemical complementarities, “hot spots”, as well as an extremely low mutation rate that give us key knowledge to influence these PPIs. Exogenous regulation of PPIs is aimed at both inhibiting the assembly and/or destabilization of protein complexes. Often, the design of such modulators is associated with some specific problems in targeted delivery, cell penetration and proteolytic stability, as well as selective binding to cellular targets. Recent progress in interfacial peptide design has been achieved in solving all these difficulties and has provided a good efficiency in preclinical models (in vitro and in vivo). The most promising peptide-containing therapeutic formulations are under investigation in clinical trials. In this review, we update the current state-of-the-art in the field of interfacial peptides as potent modulators of a number of disease-related PPIs. Over the past years, the scientific interest has been focused on following clinically significant heterodimeric PPIs MDM2/p53, PD-1/PD-L1, HIF/HIF, NRF2/KEAP1, RbAp48/MTA1, HSP90/CDC37, BIRC5/CRM1, BIRC5/XIAP, YAP/TAZ–TEAD, TWEAK/FN14, Bcl-2/Bax, YY1/AKT, CD40/CD40L and MINT2/APP. Full article

(This article belongs to the Special Issue Mechanisms and Kinetics of Interactions of Biomolecules at Interfaces)

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