Temporal Fluctuations in Interparticle Interactions Drive the Formation of Transiently Stable Nanoparticle Precipitates

<p></p><p>The pH and ionic strength dependence of electrostatic interactions was explored to introduce temporal fluctuations in the strengths of interparticle interactions and choreograph a transient self-assembly response in plasmonic nanoparticles. The assembly process was triggered by the electrostatic attraction between positively-charged gold nanoparticles (AuNPs) and an aggregating agent, ethylenediaminetetraacetic acid (EDTA). The autonomous changes in the pH and ionic strength of the solution, under the influence of atmospheric CO₂, weaken the aggregating ability of EDTA and initiate the complete disassembly of [+] AuNP - EDTA precipitates. The non-destructive way of disassembly minimizes the generation of waste, which helped in achieving some of the desirable feats in the area of dynamic self-assembly like easy removal of waste, transiently stable precipitates and negligible dampness. The chemical strategy adopted in the present work, to introduce transientness, can act as a generic tool in creating the next generation of complex matter.</p><br><p></p>

Temporal Fluctuations in Interparticle Interactions Drive the Formation of Transiently Stable Nanoparticle Precipitates

<p></p><p>The pH and ionic strength dependence of electrostatic interactions was explored to introduce temporal fluctuations in the strengths of interparticle interactions and choreograph a transient self-assembly response in plasmonic nanoparticles. The assembly process was triggered by the electrostatic attraction between positively-charged gold nanoparticles (AuNPs) and an aggregating agent, ethylenediaminetetraacetic acid (EDTA). The autonomous changes in the pH and ionic strength of the solution, under the influence of atmospheric CO₂, weaken the aggregating ability of EDTA and initiate the complete disassembly of [+] AuNP - EDTA precipitates. The non-destructive way of disassembly minimizes the generation of waste, which helped in achieving some of the desirable feats in the area of dynamic self-assembly like easy removal of waste, transiently stable precipitates and negligible dampness. The chemical strategy adopted in the present work, to introduce transientness, can act as a generic tool in creating the next generation of complex matter.</p><br><p></p>

Thermodynamics of Amyloid Fibril Formation from Chemical Depolymerization

Amyloid fibrils are homo-molecular protein polymers that play an important role in disease and biological function. While much is known about their kinetics and mechanisms of formation, the origin and magnitude of their thermodynamic stability has received significantly less attention. This is despite the fact that the thermodynamic stability of amyloid fibrils is an important determinant of their lifetimes and processing in vivo. Here we use depolymerization by chemical denaturants of amyloid fibrils of two different proteins (PI3K-SH3 and glucagon) at different concentrations and show that the previously applied linear polymerization model is an oversimplification that does not capture the concentration dependence of chemical depolymerization of amyloid fibrils. We show that cooperative polymerization, which is compatible with the picture of amyloid formation as a nucleated polymerization process, is able to quantitatively describe the thermodynamic data. We use this combined experimental and conceptual framework in order to probe the ionic strength<br>dependence of amyloid fibril stability. In combination with previously published data on the ionic strength dependence of amyloid fibril growth kinetics, our results provide strong evidence for the product-like nature of the transition state of amyloid fibril growth.

Thermodynamics of Amyloid Fibril Formation from Chemical Depolymerization

Amyloid fibrils are homo-molecular protein polymers that play an important role in disease and biological function. While much is known about their kinetics and mechanisms of formation, the origin and magnitude of their thermodynamic stability has received significantly less attention. This is despite the fact that the thermodynamic stability of amyloid fibrils is an important determinant of their lifetimes and processing in vivo. Here we use depolymerization by chemical denaturants of amyloid fibrils of two different proteins (PI3K-SH3 and glucagon) at different concentrations and show that the previously applied linear polymerization model is an oversimplification that does not capture the concentration dependence of chemical depolymerization of amyloid fibrils. We show that cooperative polymerization, which is compatible with the picture of amyloid formation as a nucleated polymerization process, is able to quantitatively describe the thermodynamic data. We use this combined experimental and conceptual framework in order to probe the ionic strength<br>dependence of amyloid fibril stability. In combination with previously published data on the ionic strength dependence of amyloid fibril growth kinetics, our results provide strong evidence for the product-like nature of the transition state of amyloid fibril growth.

Computational investigation of protein surface polarity and pH-dependence: application to antibodies shows that antibody-antigen interfaces tend to be relatively polar

Protein instability leads to reversible self-association and irreversible aggregation which is a major concern for developing new biopharmaceutical leads. Protein solution behaviour is dictated by the physicochemical properties of the protein and the solution. Optimising protein solutions through experimental screens and targeted protein engineering can be a difficult and time consuming process. Here, we describe development of the protein-sol web server, which was previously restricted to protein solubility prediction from amino acid sequence. Tools are presented for calculating and mapping patches of hydrophobicity and charge on the protein surface. In addition, predictions of folded state stability and net charge are displayed as a heatmap for a range of pH and ionic strength conditions. Tools are evaluated in the context of antibodies, their fragments and interactions. Surprisingly, antibody-antigen interfaces are, on average, at least as polar as Fab surfaces. This benchmarking process provides the user with thresholds with which to assess non-polar surface patches, and possible solubility implications, in proteins of interest. Stability heatmaps compare favourably with experimental data for CH2 and CH3 domains. Display and quantification of surface polarity and pH / ionic strength dependence will be useful generally for investigation of protein biophysics.

Step-by-step deposition of type B gelatin and tannic acid displays a peculiar ionic strength dependence at pH 5

Tannic acid (TA), among other polyphenols, interacts strongly with proteins, in particular proline rich proteins, a mechanism which is at the origin of mouth astringency.