Abstract
Understanding diffusion of intrinsically disordered proteins (IDPs) under crowded environments is of ubiquitous importance to modelling related dynamics in biological systems. In the present work, we proposed a theoretical framework to study the diffusion behavior of IDPs in polymer solutions. IDP is modeled as an ensemble of particles with a wide range of gyration radius subject to Flory-Fisk distribution, where the collapse effect which leads to the shrink of IDP due to polymer crowding is included. The diffusion coefficient of IDP is calculated as the average, denoted by 〈D〉, over the values of the particle samples. By properly incorporating the scaling relations for diffusion coefficient of nanoparticle (NP) in polymer solutions, we are able to evaluate 〈D〉 straightforwardly and reveal the disorder and collapse effects on IDP’s diffusion in an explicit manner. Particular attentions are paid on comparison between the diffusion coefficient of an IDP and that of a NP. Results demonstrate that both disorder and collapse can enhance IDP diffusion rate. Our analysis shows that the crossover behavior reported by experiments can be actually a general phenomenon, namely, while a NP with smaller size than that of an IDP diffuses faster in simple solutions, the IDP may become the faster one under crowded conditions. We apply our theory to analyze the diffusion of several types of IDP in a few different polymer solutions. Good agreements between the theoretical results and the experimental data are obtained.
Highlights
IntroductionThere is a growing interest to understand how proteins move through physiological media, which are heterogeneous and highly crowded by various macromolecules, such as proteins, DNA, ribosomes and membranes with certain concentrations and large volume occupation.[1,2,3,4,5,6] Crowding in biological cells exerts a modulating effect on biomolecular structure and dynamics, including protein stability, folding, binding, oligomerization, etc.[7,8,9] Diffusion of proteins in crowded environments is a benchmark problem of a wide variety relevant kinetics of biomolecules, such as drug delivery, signal transduction, protein-protein association and so on.[10,11,12,13,14] Besides, diffusion fuels a plethora of vital activities in living cells
We have proposed a theoretical modeling for the diffusion of Intrinsically disordered proteins (IDPs) in crowding polymer solutions
Two main characteristics of IDP have been highlighted: One is the disorder effect that an IDP may jump between different configurations during the long-time diffusion process; the other is the collapse effect that an IDP may shrink due to the crowded environment
Summary
There is a growing interest to understand how proteins move through physiological media, which are heterogeneous and highly crowded by various macromolecules, such as proteins, DNA, ribosomes and membranes with certain concentrations and large volume occupation.[1,2,3,4,5,6] Crowding in biological cells exerts a modulating effect on biomolecular structure and dynamics, including protein stability, folding, binding, oligomerization, etc.[7,8,9] Diffusion of proteins in crowded environments is a benchmark problem of a wide variety relevant kinetics of biomolecules, such as drug delivery, signal transduction, protein-protein association and so on.[10,11,12,13,14] Besides, diffusion fuels a plethora of vital activities in living cells. Experiments and simulations have shown that IDP will be compacted in solutions with increasing of crowding agent’s concentration and size, subject to the so-called collapse effect.[25,26,27,28] Due to the structure flexibility, both chemical and physical properties of an IDP are very
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