Impact of polydispersity and confinement on diffusion in hydrodynamically interacting colloidal suspensions

González, Emma; Aponte-Rivera, Christian; Zia, Roseanna N.

doi:10.1017/jfm.2021.563

Cited by 13 publications

(17 citation statements)

References 70 publications

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“…Further, our model provides a basis for investigating how protein behavior varies generally with colloidal-scale molecular and cellular properties. For example, confinement (Aponte-Rivera and Zia, 2022; Aponte-Rivera et al, 2018; Gonzalez et al, 2021) (e.g., by a cell membrane) and size polydispersity (Asakura and Oosawa, 1954; Gonzalez et al, 2021; Maheshwari et al, 2022) can induce structural correlations between molecules, which we might expect to augment co-localization driven by UW-PPIs.…”

Section: Discussionmentioning

confidence: 99%

Ultra-weak protein-protein interactions can modulate proteome-wide searching and binding

Hofmann

Maheshwari

Sunol

et al. 2022

Preprint

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Research on protein-protein interaction (PPIs) tends to focus on high affinity interactions. Weaker interactions (Kd > 1 µM) recently understood as contributing to intracellular phase separation suggest that even-weaker PPIs might also matter in as-yet unknown ways. However, ultra-weak PPIs (Kd > 1 mM) are not readily accessible by in vivo techniques. Here we use protein electrostatics to estimate PPI strengths and spatially-resolved dynamic simulations to investigate the potential impacts of ultra-weak PPIs within dense protein suspensions. We find that ultra-weak PPIs can drive formation of transient clusters that last long enough to enable enzyme-catalyzed reactions and accelerate the sampling of protein associations. We apply our method to Mycoplasma genitalium , finding that ultra-weak PPIs should be ubiquitous among cytoplasmic proteins. We also predict that the proteome-wide interactome can be shifted to favor 'binding-dominant' ultra-weak PPIs via the introduction of a few charged protein complexes. We speculate that ultra-weak PPIs could contribute to cellular fitness by facilitating sampling and colloidal-scale transport of proteins involved in biological processes, including protein synthesis.

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Section: Discussionmentioning

confidence: 99%

Ultra-weak protein-protein interactions can modulate proteome-wide searching and binding

Hofmann

Maheshwari

Sunol

et al. 2022

Preprint

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“…More specifically, attractive interactions between the ribosomal L7/L12 domain and ternary complexes (Mustafi and Weisshaar, 2018) or between cognate ternary complexes and mRNA (Grosjean and Chantrenne, 1980) could have the effect of pre-loading or pre-sorting ternary complexes. As a second example, hydrodynamic models of small and large particles confined in a cavity show that both types of particles tend to concentrate near the cavity surface with minor impact on the mobility of small particles (Gonzalez et al, 2021), indicating that ternary complexes and ribosomes may concentrate by the cell membrane (not currently represented in our model) and effectively improve in proximity to each other.…”

Section: Discussionmentioning

confidence: 97%

“…Modeling such forces, in addition to other molecular details like shape, softness, flexibility, and site-specificity, is becoming possible with other algorithms such as Stokesian dynamics for large or confined systems (Aponte-Rivera et al, 2018;Gonzalez et al, 2021;Maheshwari et al, 2019;Ouaknin et al, 2021;Zakhari et al, 2017), but will require substantial integration and iteration with experiments as well as improvements in computational efficiency to achieve accurate simulations over the timescales of cellular behavior (Endy and Brent, 2001). Capturing detailed molecular dynamics, such as those involved with ternary complex-ribosome binding and reactions, will also necessitate multi-scale modeling and experimentation from atomic to cellular scales.…”

Section: Discussionmentioning

confidence: 99%

Colloidal physics modeling reveals how per-ribosome productivity increases with growth rate inE. coli

Maheshwari

González

Sunol

et al. 2021

Preprint

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SummaryFaster growing cells must make proteins more quickly. This occurs in part through increasing total ribosome abundance. However, the productivity of individual ribosomes also increases, almost doubling via an unknown mechanism. To investigate, we model both physical transport and chemical reactions among ensembles of individual molecules involved in translation elongation in Escherichia coli. We predict that the Damköhler number, the ratio of transport latency to reaction latency, for translation elongation is ~4; physical transport of individual ternary complexes accounts for ~80% of elongation latency. We also model how molecules pack closer together as growth quickens. Although denser cytoplasm both decreases transport distances and hinders motion, we predict that decreasing distance wins out, offering a simple mechanism for how individual elongating ribosomes become more productive as growth quickens. We also quantify how crowding imposes a physical limit on the performance of self-mixing molecular systems and likely undergirds cellular behavior more broadly.

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“…Computational studies showed similar effects influencing the self-diffusion close to interfaces. 4 However, the existing explicit comparisons between experiment and colloid theory do not sufficiently address the genuine effects of polydispersity, for example, the experimental results in ref ( 39 ) can still be approximately described by an effective monodisperse system due to the experimental restriction to only one type of tracer protein.…”

Section: Introductionmentioning

confidence: 99%

“…Understanding the diffusive transport of macromolecules in the polydisperse and crowded ensemble within the aqueous intracellular fluid of living cells is crucial to understand their function. , Polydispersity − and crowding − are, thus, subject to numerous theoretical, simulation, ,, and experimental studies. Both living cells or even small organisms in their entire complexity − and settings with different degrees of simplification have been explored using spectroscopic methods, such as nuclear magnetic resonance (NMR), , Mössbauer spectroscopy, and fluorescence correlation spectroscopy. − Drastically simplified model systems with well-defined and adjustable configuration parameters can help to test models, many of which are derived from colloid physics. − …”

Section: Introductionmentioning

confidence: 99%

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

Beck

Grimaldo²,

López

et al. 2022

J. Phys. Chem. B

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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.

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Impact of polydispersity and confinement on diffusion in hydrodynamically interacting colloidal suspensions

Abstract: Abstract

Cited by 13 publications

References 70 publications

Ultra-weak protein-protein interactions can modulate proteome-wide searching and binding

Ultra-weak protein-protein interactions can modulate proteome-wide searching and binding

Colloidal physics modeling reveals how per-ribosome productivity increases with growth rate inE. coli

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

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