Probing protein aggregation with quartz crystal microbalances.

The supra-molecular self-assembly of peptides and proteins is a process which underlies a range of normal and aberrant biological pathways in nature, but one which remains challenging to monitor in a quantitative way. We discuss the experimental details of an approach to this problem which involves the direct measurement in vitro of mass changes of the aggregates as new molecules attach to them. The required mass sensitivity can be achieved by the use of a quartz crystal transducer-based microbalance. The technique should be broadly applicable to the study of protein aggregation, as well as to the identification and characterisation of inhibitors and modulators of this process.

Scalable robustness for consensus protocols with heterogeneous dynamics

It is shown in the paper how robustness can be guaranteed for consensus protocols with heterogeneous dynamics in a scalable and decentralized way i.e. by each agent satisfying a test that does not require knowledge of the entire network. Random graph examples illustrate that the proposed certificates are not conservative for classes of large scale networks, despite the heterogeneity of the dynamics, which is a distinctive feature of this work. The conditions hold for symmetric protocols and more conservative stability conditions are given for general nonsymmetric interconnections. Nonlinear extensions in an IQC framework are finally discussed. Copyright © 2005 IFAC.

Electrostatic effects in filamentous protein aggregation.

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules.