Short-Time Transport Properties of Bidisperse Suspensions of Immunoglobulins and Serum Albumins Consistent with a Colloid Physics Picture

Abstract

The crowded environment of biological systems such as the interior of living cells is occupied by macromolecules with a broad size distribution. This situation of polydispersity might influence the dependence of the diffusive dynamics of a given tracer macromolecule in a monodisperse solution on its hydrodynamic size and on the volume fraction. The resulting size dependence of diffusive transport crucially influences the function of a living cell. Here, we investigate a simplified model system consisting of two constituents in aqueous solution, namely, of the proteins bovine serum albumin (BSA) and bovine polyclonal gamma-globulin (Ig), systematically depending on the total volume fraction and ratio of these constituents. From high-resolution quasi-elastic neutron spectroscopy, the separate apparent short-time diffusion coefficients for BSA and Ig in the mixture are extracted, which show substantial deviations from the diffusion coefficients measured in monodisperse solutions at the same total volume fraction. These deviations can be modeled quantitatively using results from the short-time rotational and translational diffusion in a two-component hard sphere system with two distinct, effective hydrodynamic radii. Thus, we find that a simple colloid picture well describes short-time diffusion in binary mixtures as a function of the mixing ratio and the total volume fraction. Notably, the self-diffusion of the smaller protein BSA in the mixture is faster than the diffusion in a pure BSA solution, whereas the self-diffusion of Ig in the mixture is slower than in the pure Ig solution.

A proteome scale study reveals how plastic surfaces and agitation promote protein aggregation

“…It was shown experimentally and by modelling that the diffusion of large proteins at interfaces is reduced compared to small ones. This mechanism could account for a longer time of residence and hence a higher number of protein complexes at the A/L interface, where they are subject to compression and elongation forces favouring further destabilization and aggregation 44 .…”

Effects of flexibility in coarse-grained models for bovine serum albumin and immunoglobulin G

“…Recent work has investigated diffusion in a binary mixture of BSA and IgG, with an interpretation in terms of a binary hard sphere system being quite sensible. 86 An explicit investigation using the coarse-grained models could provide us with more insight into these findings. In addition, our CG model for BSA together with the established CG model for IGG opens opportunities for more realistic simulations of dynamical processes in solutions modeling blood as BSA can be used as substitute for human serum albumin (HSA), which is the most abundant protein in blood.…”

Notes on Fitting and Analysis Frameworks for QENS Spectra of (Soft) Colloid Suspensions

“…Since the signal is typically dominated by incoherent scattering, the q-dependence mainly influences the different dynamic features. While this approach includes the separation of the (apparent) global diffusion from internal diffusive processes [8], the same procedure can be applied to separate the scattering signal of the crowders from the one of the protein of interest [23], the contributions of monomers and crystals [30], the contributions of two different proteins [31], or to distinguish the scattering signal of proteins from the one coming from the detergent used for purification [32].…”