Proteins at air–water and oil–water interfaces in an all-atom model

Zhao, Yani; Cieplak, Marek

doi:10.1039/c7cp03829a

Cited by 21 publications

(25 citation statements)

References 29 publications

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“…The aggregation behavior of mAbs under hydrodynamic stress is clearly affected by a variety of parameters. The defined nature of the flow environment in the EFD can allow the effects of protein sequence and concentration, surface chemistry (Biddlecombe et al, 2007), strain rate, shear rate and the total exposure time on the observed aggregation to be determined in the absence of other confounding factors such as air-water interfaces or the action of stirring (Fleischman et al, 2017;Joubert et al, 2011;Kiese et al, 2008;Tamizi & Jouyban, 2016;Zhao & Cieplak, 2017). Furthermore, by subjecting mAbs to hydrodynamic stress in different buffer conditions, we have highlighted that the choice of excipient can be another crucial factor in influencing the extent of aggregation, opening up the possibility of using the EFD as a formulation tool.…”

Section: Discussionmentioning

confidence: 99%

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

Willis

Kumar

Dobson

et al. 2018

Biotech & Bioengineering

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Monoclonal antibodies (mAbs) currently dominate the biopharmaceutical sector due to their potency and efficacy against a range of disease targets. These proteinaceous therapeutics are, however, susceptible to unfolding, mis‐folding, and aggregation by environmental perturbations. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation, and storage. Hydrodynamic forces have also been linked to aggregation, but the ability of different flow fields (e.g., shear and extensional flow) to trigger aggregation has remained unclear. To address this question, we previously developed a device that allows the degree of extensional flow to be controlled. Using this device we demonstrated that mAbs are particularly sensitive to the force exerted as a result of this flow‐field. Here, to investigate the utility of this device to bio‐process/biopharmaceutical development, we quantify the effects of the flow field and protein concentration on the aggregation of three mAbs. We show that the response surface of mAbs is distinct from that of bovine serum albumin (BSA) and also that mAbs of similar sequence display diverse sensitivity to hydrodynamic flow. Finally, we show that flow‐induced aggregation of each mAb is ameliorated by different buffers, opening up the possibility of using the device as a formulation tool. Perturbation of the native state by extensional flow may thus allow identification of aggregation‐resistant mAb candidates, their bio‐process parameters and formulation to be optimized earlier in the drug‐discovery pipeline using sub‐milligram quantities of material.

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Section: Discussionmentioning

confidence: 99%

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

Willis

Kumar

Dobson

et al. 2018

Biotech & Bioengineering

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“…Over the years, and across different fields of research, it has been shown that the air-water interface (AWI) can be a hostile environment for proteins and macromolecular complexes (Glaeser and Han, 2017;Zhao and Cieplak, 2017;Gerhardt et al, 2014;Wiesbauer et al, 2013). In a typical cryoEM grid preparation both sides of the thin film are exposed to the AWI, creating a very high surface-area-to-volume ratio.…”

Section: Introductionmentioning

confidence: 99%

Need for Speed: Examining Protein Behavior during CryoEM Grid Preparation at Different Timescales

et al. 2020

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Summary A host of new technologies are under development to improve the quality and reproducibility of cryoelectron microscopy (cryoEM) grid preparation. Here we have systematically investigated the preparation of three macromolecular complexes using three different vitrification devices (Vitrobot, chameleon, and a time-resolved cryoEM device) on various timescales, including grids made within 6 ms (the fastest reported to date), to interrogate particle behavior at the air-water interface for different timepoints. Results demonstrate that different macromolecular complexes can respond to the thin-film environment formed during cryoEM sample preparation in highly variable ways, shedding light on why cryoEM sample preparation can be difficult to optimize. We demonstrate that reducing time between sample application and vitrification is just one tool to improve cryoEM grid quality, but that it is unlikely to be a generic “silver bullet” for improving the quality of every cryoEM sample preparation.

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“…The conventional picture of hydrophobins as having a hydrophobic face that drives interfacial adsorption leads to the assumption that this patch points into the hydrophobic media. This has been demonstrated by atomistic MD simulations of the class-II hydrophobins HFBI [81,82] and HFBII [83] at the air-water interface. In both cases, the proteins adsorb onto the air-water interface with the patch pointing into the vacuum (air) region.…”

Section: Hydrophobin Behaviour At Fluid (Air-water or Oil-water) Intementioning

confidence: 87%

Molecular Dynamics Simulation of Protein Biosurfactants

Cheung

Samantray

2018

Colloids and Interfaces

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Surfaces and interfaces are ubiquitous in nature and are involved in many biological processes. Due to this, natural organisms have evolved a number of methods to control interfacial and surface properties. Many of these methods involve the use of specialised protein biosurfactants, which due to the competing demands of high surface activity, biocompatibility, and low solution aggregation may take structures that differ from the traditional head–tail structure of small molecule surfactants. As well as their biological functions, these proteins have also attracted interest for industrial applications, in areas including food technology, surface modification, and drug delivery. To understand the biological functions and technological applications of protein biosurfactants, it is necessary to have a molecular level description of their behaviour, in particular at surfaces and interfaces, for which molecular simulation is well suited to investigate. In this review, we will give an overview of simulation studies of a number of examples of protein biosurfactants (hydrophobins, surfactin, and ranaspumin). We will also outline some of the key challenges and future directions for molecular simulation in the investigation of protein biosurfactants and how this can help guide future developments.

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Proteins at air–water and oil–water interfaces in an all-atom model

Cited by 21 publications

References 29 publications

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

Using extensional flow to reveal diverse aggregation landscapes for three IgG1 molecules

Need for Speed: Examining Protein Behavior during CryoEM Grid Preparation at Different Timescales

Molecular Dynamics Simulation of Protein Biosurfactants

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