Ionic Strength Affects Tertiary Structure and Aggregation Propensity of a Monoclonal Antibody Adsorbed to Silicone Oil–Water Interfaces

2013 ◽  
Vol 102 (2) ◽  
pp. 429-440 ◽  
Author(s):  
Alana Gerhardt ◽  
Kurt Bonam ◽  
Jared S. Bee ◽  
John F. Carpenter ◽  
Theodore W. Randolph
Keyword(s):  
Monoclonal Antibody ◽  
Ionic Strength ◽  
Tertiary Structure ◽  
Silicone Oil ◽  
Aggregation Propensity ◽  
Oil Water

Gelation of a Monoclonal Antibody at the Silicone Oil–Water Interface and Subsequent Rupture of the Interfacial Gel Results in Aggregation and Particle Formation

2015 ◽  
Vol 104 (4) ◽  
pp. 1282-1290 ◽  
Author(s):  
Shyam B. Mehta ◽  
Rachael Lewus ◽  
Jared S. Bee ◽  
Theodore W. Randolph ◽  
John F. Carpenter
Keyword(s):  
Monoclonal Antibody ◽  
Silicone Oil ◽  
Particle Formation ◽  
Water Interface ◽  
Oil Water

scholarly journals Monoclonal Antibody Aggregation near Silicone Oil–Water Interfaces

Langmuir ◽  
2021 ◽  
Vol 37 (4) ◽  
pp. 1386-1398
Author(s):  
Rajat Dandekar ◽  
Arezoo M. Ardekani
Keyword(s):  
Monoclonal Antibody ◽  
Silicone Oil ◽  
Oil Water

Effect of Ionic Strength on the Aggregation Propensity of Aβ1-42 Peptide: An In-silico Study

2020 ◽  
Vol 14 (3) ◽  
pp. 216-226
Author(s):  
Priyanka Borah ◽  
Venkata S.K. Mattaparthi
Keyword(s):  
Diffusion Coefficient ◽  
Ionic Strength ◽  
Marked Effect ◽  
Computational Study ◽  
Conformational Dynamics ◽  
Rapid Change ◽  
Md Simulations ◽  
Radius Of Gyration ◽  
Aggregation Propensity ◽  
In Silico Study

Background: Aggregation of misfolded proteins under stress conditions in the cell might lead to several neurodegenerative disorders. Amyloid-beta (Aβ1-42) peptide, the causative agent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, forming aggregated amyloid plaques. This is influenced by factors such as pH, temperature, metal ions, mutation of residues, and ionic strength of the solution. There are several studies that have highlighted the importance of ionic strength in affecting the folding and aggregation propensity of Aβ1-42 peptide. Objective: To understand the effect of ionic strength of the solution on the aggregation propensity of Aβ1-42 peptide, using computational approaches. Materials and Methods: In this study, Molecular Dynamics (MD) simulations were performed on Aβ1-42 peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentration of NaCl solution. To prepare the input files for the MD simulations, we have used the Amberff99SB force field. The conformational dynamics of Aβ1-42 peptide monomer in different ionic strengths of the solutions were illustrated from the analysis of the corresponding MD trajectory using the CPPtraj tool. Results: From the MD trajectory analysis, we observe that with an increase in the ionic strength of the solution, Aβ1-42 peptide monomer shows a lesser tendency to undergo aggregation. From RMSD and SASA analysis, we noticed that Aβ1-42 peptide monomer undergoes a rapid change in conformation with an increase in the ionic strength of the solution. In addition, from the radius of gyration (Rg) analysis, we observed Aβ1-42 peptide monomer to be more compact at moderate ionic strength of the solution. Aβ1-42 peptide was also found to hold its helical secondary structure at moderate and higher ionic strengths of the solution. The diffusion coefficient of Aβ1-42 peptide monomer was also found to vary with the ionic strength of the solution. We observed a relatively higher diffusion coefficient value for Aβ1-42 peptide at moderate ionic strength of the solution. Conclusion: Our findings from this computational study highlight the marked effect of ionic strength of the solution on the conformational dynamics and aggregation propensity of Aβ1-42 peptide monomer.

scholarly journals Fabrication of silica/PVA-co-PE nanofiber membrane for oil/water separation

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yuanli Chen ◽  
Hui Fan ◽  
Xinlin Zha ◽  
Wenwen Wang ◽  
Yi Wu ◽  
...  
Keyword(s):  
High Efficiency ◽  
Silicone Oil ◽  
Hydroxyl Groups ◽  
Water Mixture ◽  
Silica Nanospheres ◽  
Nanofiber Membrane ◽  
Water Separation ◽  
Oil Water Separation ◽  
Silica Nanostructures ◽  
Oil Water

AbstractHigh efficiency and anti-pollution oil/water separation membrane has been widely explored and researched. There are a large number of hydroxyl groups on the surface of silica, which has good wettability and can be used for oil-water separation membranes. Hydrophilic silica nanostructures with different morphologies were synthesized by changing templates and contents of trimethylbenzene (TMB). Here, silica nanospheres with radical pores, hollow silica nanospheres and worm-like silica nanotubes were separately sprayed on the PVA-co-PE nanofiber membrane (PM). The abundance of hydroxyl groups and porous structures on PM surfaces enabled the absorption of silica nanospheres through hydrogen bonds. Compared with different silica nanostructures, it was found that the silica/PM exhibited excellent super-hydrophilicity in air and underwater “oil-hating” properties. The PM was mass-produced in our lab through melt-extrusion-phase-separation technique. Therefore, the obtained membranes not only have excellent underwater superoleophobicity but also have a low-cost production. The prepared silica/PM composites were used to separate n-hexane/water, silicone oil/water and peanut oil water mixtures via filtration. As a result, they all exhibited efficient separation of oil/water mixture through gravity-driven filtration.

Potential aggregation hot spots in recombinant human keratinocyte growth factor; a computational study

2020 ◽  
Author(s):  
Mansoureh Shahbazi Dastjerdeh ◽  
Mohammad Ali Shokrgozar ◽  
Hamzeh Rahimi ◽  
Majid Golkar
Keyword(s):  
Growth Factor ◽  
Tertiary Structure ◽  
Computational Study ◽  
Keratinocyte Growth Factor ◽  
Native State ◽  
Hydrophobic Residues ◽  
Aggregation Propensity ◽  
State Aggregation ◽  
Human Keratinocyte ◽  
Aggregation Tendency

Abstract Background: Recombinant human keratinocyte growth factor is a highly aggregation-prone therapeutic protein. The high aggregation liability of rhKGF is manifested by loss of the monomeric form of the protein and accumulation of the aggregated species even at moderate temperatures. Here, we analyzed rhKGF for its vulnerability towards aggregation by detection of aggregation-prone regions (APRs) using several sequence-based computational tools including TANGO, SolubiS, ZipperDB, AGGRESCAN, Zyggregator, Camsol, PASTA, SALSA, WALTZ, SODA, Amylpred, AMYPDB, and structure-based tools including Aggrescan3D and molecular dynamics-based spatial aggregation propensity (SAP) algorithm. Results: The sequence-based prediction of APRs in rhKGF indicated that they are mainly located at positions 10-30, 40-60, 61-66, 88-120, and 130-140 which are rich in β-branched aliphatic, hydrophobic, aromatic and Glutamine/Aspargine (Q/N) residues. Mapping on the rhKGF tertiary structure revealed that most of these residues including F16-R25, I43, E45, R47-I56, F61, Y62, N66, L88-E91, E108-F110, A112, N114, T131, and H133-T140 are surface-exposed in the natively folded protein which can promote aggregation without major unfolding event or the conformational change may occur in the oligomers composed of natively folded monomers. The other regions are buried in the native state and their contribution to non-native aggregation is mediated by a preceding unfolding event in the monomeric state of the protein. The structure-based prediction of APRs using SAP tool limited the number of identified APRs to the dynamically-exposed hydrophobic residues including V12, A50, V51, L88, I89, L90, I118, L135, and I139 mediating the native-state aggregation. Conclusion: Our analysis of APRs in rhKGF identified the regions determining the intrinsic aggregation propensity in both folded (native) and unfolded state of the protein. These regions are the candidate positions for engineering the rhKGF sequence to reduce its aggregation tendency.

Viscous Oil-Water Flow in a Microchannel: Flow Patterns and Flow Development

2010 ◽  
Author(s):  
Hooman Foroughi ◽  
Masahiro Kawaji
Keyword(s):  
Water Flow ◽  
Silicone Oil ◽  
Flow Characteristics ◽  
Flow Patterns ◽  
Fused Silica ◽  
Water Mixture ◽  
Injection Point ◽  
Viscous Oil ◽  
Wide Range ◽  
Oil Water

The flow characteristics of a highly viscous oil and water mixture in a circular microchannel have been investigated. Water and silicone oil with a viscosity of 863 mPa.s were injected into a fused silica microchannel with a diameter of 250 μm. Before each experiment, the microchannel was initially saturated with either oil or water. In the initially oil-saturated case, different liquid-liquid flow patterns were observed and classified over a wide range of oil and water flow rates. As a special case, the flow of water at zero oil flow rate in a microchannel initially filled with silicone oil was also studied. When the microchannel was initially saturated with water, the oil formed a jet in water at the injection point but developed an instability at the oil-water interface downstream and eventually broke up into droplets.

Study of wetting at the silicone oil/water/fibre interface

1999 ◽  
Vol 147 (3) ◽  
pp. 317-329 ◽  
Author(s):  
Anne Perwuelz ◽  
Teresa Novais De Olivera ◽  
Claude Caze
Keyword(s):  
Silicone Oil ◽  
Oil Water

scholarly journals Accessibility of epitopes on fibrin clots and fibrinogen gels

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1469-1475 ◽  
Author(s):  
R Procyk ◽  
B Kudryk ◽  
S Callender ◽  
B Blomback
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Ionic Strength ◽  
Factor Xiii ◽  
Imaging Agent ◽  
Low Ionic Strength ◽  
Clot Structure ◽  
Radiolabeled Antibodies ◽  
Fibrin Clots

Abstract Radiolabeled antibodies were perfused into fibrin clots and fibrinogen gels formed in vitro to assess the reactivity of selected epitopes. An antifibrinogen monoclonal antibody (MoAb) (antibody 1D4/xl-f), directed against an epitope in the A alpha-chain C-terminal region (A alpha 241– 476), bound to 35% of the epitope in crosslinked fibrin clots and 37% of the same epitope in factor XIII-induced fibrinogen gel networks. A different MoAb (4–2/xl-f, anti gamma 392–406) bound to only 7% of the epitope in both fibrin and fibrinogen gels. As expected, an antifibrin MoAb (antibody T2G1, antiB beta 15–21) did not bind to fibrinogen gels, but bound to fibrin, although to only 14% of the available T2G1- reactive epitopes. An antibody that does not recognize fibrin (antibody 1–8C6, antiB beta 1–21) predictably did not bind to fibrin clots and bound to 35% of the 1–8C6 epitopes present in fibrinogen gels, a level of binding also observed with antibody T2G1 and fibrinogen gels only after the latter were treated with thrombin. T2G1 epitope expression was affected much more than 1D4/xl-f epitope expression in clots formed in buffers of high or low ionic strength, conditions known to influence clot structure. Studies on the availability, in quantitative terms, of the T2G1-reactive epitope in fibrin clots is of particular importance because this antibody is currently being used in clinical trials as a clot imaging agent.

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