Effects of polydisperse crowders on aggregation reactions: A molecular thermodynamic analysis

Shah, Dhawal; Tan, Aik Lee; Ramakrishnan, Vigneshwar; Jiang, Jianwen; Rajagopalan, Raj

doi:10.1063/1.3549906

Cited by 12 publications

(20 citation statements)

References 43 publications

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“…There, the crowding induced changes in the diffusion of signalling molecules is expected to impact gene regulation and metabolism [127] and also alter active transport properties [21,33,34,128]. Other extensions of the current model include polydisperse static and dynamic crowders [129][130][131], cylindrical domains mimicking a typical bacterial shape [55,132], specific and non-specific tracer-crowder interactions [55,61], three-dimensional computer simulations, a variable tracer size, as well as deformable and non-spherical crowding particles [133,134].…”

Section: Discussionmentioning

confidence: 99%

Anomalous, non-Gaussian tracer diffusion in crowded two-dimensional environments

et al. 2016

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A topic of intense current investigation pursues the question of how the highly crowded environment of biological cells affects the dynamic properties of passively diffusing particles. Motivated by recent experiments we report results of extensive simulations of the motion of a finite sized tracer particle in a heterogeneously crowded environment made up of quenched distributions of monodisperse crowders of varying sizes in finite circular two-dimensional domains. For given spatial distributions of monodisperse crowders we demonstrate how anomalous diffusion with strongly non-Gaussian features arises in this model system. We investigate both biologically relevant situations of particles released either at the surface of an inner domain or at the outer boundary, exhibiting distinctly different features of the observed anomalous diffusion for heterogeneous distributions of crowders. Specifically we reveal an asymmetric spreading of tracers even at moderate crowding. In addition to the mean squared displacement (MSD) and local diffusion exponent we investigate the magnitude and the amplitude scatter of the time averaged MSD of individual tracer trajectories, the non-Gaussianity parameter, and the van Hove correlation function. We also quantify how the average tracer diffusivity varies with the position in the domain with a heterogeneous radial distribution of crowders and examine the behaviour of the survival probability and the dynamics of the tracer survival probability. Inter alia, the systems we investigate are related to the passive transport of lipid molecules and proteins in two-dimensional crowded membranes or the motion in colloidal solutions or emulsions in effectively two-dimensional geometries, as well as inside supercrowded, surface adhered cells.

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Section: Discussionmentioning

confidence: 99%

Anomalous, non-Gaussian tracer diffusion in crowded two-dimensional environments

et al. 2016

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“…These experiments showed that when comparing the sum of effects of each of the crowders alone with the effect of a mixture of crowding agents, the later have a synergistic effect on protein stability [49–52]. However, excluding a theoretical treatment [53], the effect of defined mixed crowding agents on association of protein complexes has not been reported. Along the same lines, cell extracts and bacterial lysates were used to achieve an improved representation of the in‐cell composition of molecules.…”

Section: In Vitro Crowding Studiesmentioning

confidence: 99%

Formation of protein complexes in crowded environments – From in vitro to in vivo

2013

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a b s t r a c tTraditionally, biochemical studies are performed in dilute homogenous solutions, which are very different from the dense mixture of molecules found in cells. Thus, the physiological relevance of these studies is in question. This recognition motivated scientists to formulate the effect of crowded solutions in general, and excluded volume in particular, on biochemical processes. Using polymers or proteins as crowders, it was shown that while crowding tends to significantly enhance the formation of complexes containing many subunits, dimerizations are only mildly affected. Computer simulations, together with experimental evidence, indicate soft interactions and diffusion as critical factors that operate in a concerted manner with excluded volume to modulate protein binding. Yet, these approaches do not truly mimic the cellular environment. In vivo studies may overcome this shortfall. The few studies conducted thus far suggest that in cells, binding and folding occur at rates close to those determined in dilute solutions. Obtaining quantitative biochemical information on reactions inside living cells is currently a main challenge of the field, as the complexity of the intracellular milieu was what motivated crowding research to begin with.

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“…It has been shown on numerous occasions that protein conformation 10,11 , folding 12–15 , association 16–18 , dynamics 19,20 , and aggregation 21,22 are highly affected by the excluded volume effect. These results can be interpreted as entropic effects because of the confinement 23–25 and as thermodynamic effects as a result of deviations from ideal solution behavior 26,27 . Although disregarded by most in vitro studies, it has also been shown that the presence of crowding is essential for DNA transcription and replication to correlate the in vitro results to in vivo counterparts 28 .…”

Section: Introductionmentioning

confidence: 97%

Conformational Sampling of Peptides in the Presence of Protein Crowders from AA/CG-Multiscale Simulations

et al. 2012

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Macromolecular crowding is recognized as an important factor influencing folding and conformational dynamics of proteins and nucleic acids. Previous views of crowding have focused on the mostly entropic volume exclusion effect of crowding but recent studies are indicating the importance of enthalpic effects, in particular changes in electrostatic interactions due to crowding. Here, temperature replica exchange molecular dynamics simulations of trp-cage and melittin in the presence of explicit protein crowders are presented to further examine the effect of protein crowders on peptide dynamics. The simulations involve a three-component multiscale modeling scheme where the peptides are represented at atomistic level, the crowder proteins at a coarse-grained level, and the surrounding aqueous solvent as implicit solvent. This scheme optimally balances a physically realistic description for the peptide with computational efficiency. The multiscale simulations were compared with simulations of the same peptides in different dielectric environments with dielectric constants ranging from 5 to 80. It is found that the sampling in the presence of the crowders resembles sampling with reduced dielectric constants between 10 and 40. Furthermore, diverse conformational ensembles are generated in the presence of crowders including partially unfolded states for trp-cage. These findings emphasize the importance of enthalpic interactions over volume exclusion effects in describing the effects of cellular crowding.

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Effects of polydisperse crowders on aggregation reactions: A molecular thermodynamic analysis

Cited by 12 publications

References 43 publications

Anomalous, non-Gaussian tracer diffusion in crowded two-dimensional environments

Anomalous, non-Gaussian tracer diffusion in crowded two-dimensional environments

Formation of protein complexes in crowded environments – From in vitro to in vivo

Conformational Sampling of Peptides in the Presence of Protein Crowders from AA/CG-Multiscale Simulations

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