Potential and limits of a colloid approach to protein solutions.

Anna Stradner,Peter Schurtenberger

doi:10.1039/c9sm01953g

Abstract

Looking at globular proteins with the eyes of a colloid scientist has a long tradition, in fact a significant part of the early colloid literature was focused on protein solutions. However, it has also been recognized that proteins are much more complex than the typical hard sphere-like synthetic model colloids. Proteins are not perfect spheres, their interaction potentials are in general not isotropic, and using theories developed for such particles are thus clearly inadequate in many cases. In this perspective article, we now take a closer look at the field. In particular, we reflect on the fact that modern colloid science has been undergoing a tremendous development, where a multitude of novel systems have been developed in the lab and in silico. During the last decade we have seen a rapidly increasing number of reports on the synthesis of anisotropic, patchy and/or responsive synthetic colloids, that start to resemble their complex biological counterparts. This experimental development is also reflected in a corresponding theoretical and simulation effort. The experimental and theoretical toolbox of colloid science has thus rapidly expanded, and there is obviously an enormous potential for an application of these new concepts to protein solutions, which has already been realized and harvested in recent years. In this perspective article we make an attempt to critically discuss the exploitation of colloid science concepts to better understand protein solutions. We not only consider classical applications such as the attempt to understand and predict solution stability and phase behaviour, but also discuss new challenges related to the dynamics, flow behaviour and liquid-solid transitions found in concentrated or crowded protein solutions. It not only aims to provide an overview on the progress in experimental and theoretical (bio)colloid science, but also discusses current shortcomings in our ability to correctly reproduce and predict the structural and dynamic properties of protein solutions based on such a colloid approach.

Highlights

PerspectiveSince these pioneering developments in the mid 90’s, we have seen a renaissance in the use of the experimental and theoretical toolbox of colloid science in order to understand various solution properties of globular proteins
While protein phase diagrams and crystallization was initially in the focus, this colloid approach to proteins was subsequently extended to a much wider range of topics that included protein selfassembly and aggregation, the stability of crowded protein solutions and mixtures, and the dynamics of strongly interacting protein solutions.[20,21,22,23,24,25,26,27,28,29,30,31]. This approach has recently been questioned in an article by Sarangapani et al.,[32] where the authors concluded that the proteins’ capacity to adjust their shape and the nature of the interprotein interactions in response to variations in pH and concentration severely limits the usefulness of colloid models to describe the structural and dynamic properties of protein solutions
With this approach, such models can be submitted to a critical assessment. This type of approach could be extended to other proteins that display patchy interactions, and would allow for example to investigate various arrest scenarios for such systems as a function of key solution parameters. This perspective article was initially largely motivated by the notion described in ref. 33, questioning altogether the usefulness of applying colloid-like theory to protein solutions

Summary

Introduction

Since these pioneering developments in the mid 90’s, we have seen a renaissance in the use of the experimental and theoretical toolbox of colloid science in order to understand various solution properties of globular proteins. There is a clear lack of studies providing an experimental verification of the many predictions on the phase behavior of patchy colloids, and virtually no work at all is devoted to the consequences of patchy interactions on the dynamics of these suspensions This is important for an extension of the colloid approach to protein solutions beyond classical spherical particles with centrosymmetric potentials, as this currently limits our ability to use less coarse-grained models that are based on the molecular structure of proteins for a calculation of key structural and dynamic properties and their dependence on.

Protein phase behavior

Findings

Conclusions