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The Journal of Physical Chemistry. B May 2022We demonstrate a novel application of the time-temperature superposition (TTS) principle to predict solute diffusivity in glassy polymers using atomistic molecular...
We demonstrate a novel application of the time-temperature superposition (TTS) principle to predict solute diffusivity in glassy polymers using atomistic molecular dynamics simulations. Our TTS approach incorporates the Debye-Waller factor ⟨⟩, a measure of solute caging, along with concepts from thermodynamic scaling methods, allowing us to balance contributions to the dynamics from temperature and ⟨⟩ using adjustable parameters. Our approach rescales the solute mean-squared displacement curves at several temperatures into a master curve that approximates the diffusive dynamics at a reference temperature, effectively extending the simulation time scale from nanoseconds to seconds and beyond. With a set of "universal" parameters, this TTS approach predicts with reasonable accuracy in a broad range of polymer/solute systems. Using TTS greatly reduces the computational cost compared to standard MD simulations. Thus, our method offers a means to rapidly and routinely provide order-of-magnitude estimates of using simulations.
Topics: Diffusion; Molecular Dynamics Simulation; Polymers; Solutions; Temperature
PubMed: 35583328
DOI: 10.1021/acs.jpcb.2c00057 -
Biophysical Journal Dec 2017Wnt proteins are secreted, hydrophobic, lipidated proteins found in all animals that play essential roles in development and disease. Lipid modification is thought to...
Wnt proteins are secreted, hydrophobic, lipidated proteins found in all animals that play essential roles in development and disease. Lipid modification is thought to facilitate the interaction of the protein with its receptor, Frizzled, but may also regulate the transport of Wnt protein and its localization at the cell membrane. Here, by employing single-molecule fluorescence techniques, we show that Wnt proteins associate with and diffuse on the plasma membranes of living cells in the absence of any receptor binding. We find that labeled Wnt3A transiently and dynamically associates with the membranes of Drosophila Schneider 2 cells, diffuses with Brownian kinetics on flattened membranes and on cellular protrusions, and does not transfer between cells in close contact. In S2 receptor-plus (S2R+) cells, which express Frizzled receptors, membrane diffusion rate is reduced and membrane residency time is increased. These results provide direct evidence of Wnt3A interaction with living cell membranes, and represent, to our knowledge, a new system for investigating the dynamics of Wnt transport.
Topics: Animals; Cell Line; Cell Membrane; Diffusion; Drosophila; Optical Imaging; Wnt3A Protein
PubMed: 29262368
DOI: 10.1016/j.bpj.2017.08.060 -
Medical Engineering & Physics Mar 2023Effects of injection rate and tumor physiology on the diffusion of magnetic nano-particles (MNPs) and temperature profile during magnetic hyperthermia are investigated...
Effects of injection rate and tumor physiology on the diffusion of magnetic nano-particles (MNPs) and temperature profile during magnetic hyperthermia are investigated in this work. The study considers three injection rates (2.5 μL/min, 10 μL/min, and 40 μL/min), and two MNP diffusion coefficients (10 m/s and 10 m/s). The simulation of this physics has been done on 3D tumor surrounded by healthy tissue. Transient MNP distribution in tissue is evaluated using Darcy's flow model and the MNP transport (convection-diffusion) equation. The temperature profile in the tumor model is computed by solving Penne's bioheat transfer equation (PBHTE). Results show tumors with high collagen content (with low MNP diffusivity) are more restrictive towards MNP transport than tumors having low collagen content. Thus, tumors with low MNP diffusivity need a higher injection rate to increase the homogeneity of MNP concentration as well as temperature profile during thermo-therapy. Results also show that, MNP fluid injected with a higher injection rate produces a more uniform MNP concentration up to greater depth than the lower injection rate.
Topics: Nanoparticles; Hyperthermia, Induced; Neoplasms; Humans; Diffusion; Magnetic Phenomena
PubMed: 36966004
DOI: 10.1016/j.medengphy.2023.103965 -
Physical Biology Jan 2023The function of many membrane-enclosed intracellular structures relies on release of diffusing particles that exit through narrow pores or channels in the membrane. The...
The function of many membrane-enclosed intracellular structures relies on release of diffusing particles that exit through narrow pores or channels in the membrane. The rate of release varies with pore size, density, and length of the channel. We propose a simple approximate model, validated with stochastic simulations, for estimating the effective release rate from cylinders, and other simple-shaped domains, as a function of channel parameters. The results demonstrate that, for very small pores, a low density of channels scattered over the boundary is sufficient to achieve substantial rates of particle release. Furthermore, we show that increasing the length of passive channels will both reduce release rates and lead to a less steep dependence on channel density. Our results are compared to previously-measured local calcium release rates from tubules of the endoplasmic reticulum, providing an estimate of the relevant channel density responsible for the observed calcium efflux.
Topics: Calcium; Diffusion; Endoplasmic Reticulum
PubMed: 36626849
DOI: 10.1088/1478-3975/acb1ea -
The Journal of Chemical Physics Aug 2023Most biological processes in living cells rely on interactions between proteins. Live-cell compatible approaches that can quantify to what extent a given protein... (Review)
Review
Most biological processes in living cells rely on interactions between proteins. Live-cell compatible approaches that can quantify to what extent a given protein participates in homo- and hetero-oligomeric complexes of different size and subunit composition are therefore critical to advance our understanding of how cellular physiology is governed by these molecular interactions. Biomolecular complex formation changes the diffusion coefficient of constituent proteins, and these changes can be measured using fluorescence microscopy-based approaches, such as single-molecule tracking, fluorescence correlation spectroscopy, and fluorescence recovery after photobleaching. In this review, we focus on the use of single-molecule tracking to identify, resolve, and quantify the presence of freely-diffusing proteins and protein complexes in living cells. We compare and contrast different data analysis methods that are currently employed in the field and discuss experimental designs that can aid the interpretation of the obtained results. Comparisons of diffusion rates for different proteins and protein complexes in intracellular aqueous environments reported in the recent literature reveal a clear and systematic deviation from the Stokes-Einstein diffusion theory. While a complete and quantitative theoretical explanation of why such deviations manifest is missing, the available data suggest the possibility of weighing freely-diffusing proteins and protein complexes in living cells by measuring their diffusion coefficients. Mapping individual diffusive states to protein complexes of defined molecular weight, subunit stoichiometry, and structure promises to provide key new insights into how protein-protein interactions regulate protein conformational, translational, and rotational dynamics, and ultimately protein function.
Topics: Single Molecule Imaging; Diffusion; Microscopy, Fluorescence; Photobleaching; Protein Conformation
PubMed: 37589409
DOI: 10.1063/5.0155638 -
Redox Biology Apr 2022Hydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for HO as an intercellular signaling...
Hydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for HO as an intercellular signaling molecule and neuromodulator in the brain has become increasingly apparent, with evidence showing this biological oxidant to regulate neuronal polarity, connectivity, synaptic transmission and tuning of neuronal networks. This notion is supported by its ability to diffuse in the extracellular space, from source of production to target. It is, thus, crucial to understand extracellular HO concentration dynamics in the living brain and the factors which shape its diffusion pattern and half-life. To address this issue, we have used a novel microsensor to measure HO concentration dynamics in the brain extracellular matrix both in an ex vivo model using rodent brain slices and in vivo. We found that exogenously applied HO is removed from the extracellular space with an average half-life of t = 2.2 s in vivo. We determined the in vivo effective diffusion coefficient of HO to be D* = 2.5 × 10 cm s. This allows it to diffuse over 100 μm in the extracellular space within its half-life. Considering this, we can tentatively place HO within the class of volume neurotransmitters, connecting all cell types within the complex network of brain tissue, regardless of whether they are physically connected. These quantitative details of HO diffusion and half-life in the brain allow us to interpret the physiology of the redox signal and lay the pavement to then address dysregulation in redox homeostasis associated with disease processes.
Topics: Brain; Diffusion; Hydrogen Peroxide; Oxidation-Reduction; Signal Transduction
PubMed: 35101799
DOI: 10.1016/j.redox.2022.102250 -
Cell Reports Apr 2017Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one...
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates. These motifs constitute short-range positive and long-range negative feedback loops to induce Turing instability. The width and height of spatial patterns can be controlled independently by distinct reaction-diffusion processes. Therefore, multisite reversible post-translational modification can be a ubiquitous source for various patterns without requiring other complex regulations such as autocatalytic regulation of enzymes and is applicable to molecular mechanisms for inducing subcellular localization of proteins driven by post-translational modifications.
Topics: Diffusion; Enzymes; Kinesics; Models, Biological; Protein Processing, Post-Translational
PubMed: 28445735
DOI: 10.1016/j.celrep.2017.03.081 -
Journal of Mathematical Biology Oct 2022In this paper, the dynamics of a single population model with a general growth function is investigated in an advective environment. We show the existence of a...
In this paper, the dynamics of a single population model with a general growth function is investigated in an advective environment. We show the existence of a nonconstant positive steady state, and give sufficient conditions for the occurrence of a Hopf bifurcation at the positive steady state. Moreover, the theoretical results are applied to the diffusive Nicholson's blowflies and Mackey-Glass's models with advection and delay, respectively. We numerically show that the population density decreases as the increase of advection rate or death rate, and a delay-induced Hopf bifurcation is more likely to occur with small advection or low mortality rate.
Topics: Models, Biological; Population Density; Diffusion; Computer Simulation
PubMed: 36305980
DOI: 10.1007/s00285-022-01818-z -
Lab on a Chip Sep 2019Hydrogels allow for controlling the diffusion rate and amount of solute according to the hydrogel network and thus have found many applications in drug delivery,...
Hydrogels allow for controlling the diffusion rate and amount of solute according to the hydrogel network and thus have found many applications in drug delivery, biomaterials, toxicology, and tissue engineering. This paper describes a 3D-printed microfluidic chip for the straightforward partitioning of hydrogel barriers between microchannels. We use a previously-reported 3-channel architecture whereby the middle channel is filled with a hydrogel - acting like a porous barrier for diffusive transport - and the two side channels act as sink and source; the middle channel communicates with the side channels via orthogonal, small capillary channels that are also responsible for partitioning the hydrogel during filling. Our 3D-printed microfluidic chip is simple to fabricate by stereolithography (SL), inexpensive, reproducible, and convenient, so it is more adequate for transport studies than a microchip fabricated by photolithographic procedures. The chip was fabricated in a resin made of poly(ethylene glycol) diacrylate (PEG-DA) (MW = 258) (PEG-DA-258). The SL process allowed us to print high aspect ratio (37 : 1) capillary channels (27 μm-width and 1 mm-height) and enable the trapping of liquid-phase hydrogels in the hydrogel barrier middle channel. We studied the permeability of hydrogel barriers made of PEG-DA (MW = 700) (PEG-DA-700, 10% polymer content by wt. in water) - as a model of photopolymerizable barriers - and agarose (MW = 120 000, 2% polymer content by wt. in water) - as a model of thermally-gelled barriers. We measured the diffusion of fluorescein, 10k-dextran-Alexa 680 and BSA-Texas Red through these barriers. Fluorescein diffusion was observed through both 10% PEG-DA-700 and 2% agarose barriers while 10k-dextran-Alexa 680 and BSA-Texas Red diffused appreciably only through the 2% agarose hydrogel barrier. Our microfluidic chip facilitates the tuning of such barriers simply by altering the hydrogel materials. The straightforward trapping of selective barriers in 3D-printed microchannels should find wide applicability in drug delivery, tissue engineering, cell separation, and organ-on-a-chip platforms.
Topics: Diffusion; Hydrogels; Microfluidic Analytical Techniques; Polyethylene Glycols; Printing, Three-Dimensional
PubMed: 31502633
DOI: 10.1039/c9lc00535h -
Journal of Chromatography. A Sep 2020The effect of bead and ligand structure on protein adsorption was investigated for multimodal anion exchangers combining a quaternary ammonium ion group with hydrophobic...
The effect of bead and ligand structure on protein adsorption was investigated for multimodal anion exchangers combining a quaternary ammonium ion group with hydrophobic moieties: Nuvia aPrime 1 and aPrime 2, based on a 54 μm diameter polymeric bead, and Capto Adhere ImpRes and Capto Adhere, based on agarose beads 51 and 78 μm diameter, respectively. Bovine serum albumin (BSA) monomer, BSA dimer, and thyroglobulin (Tg) were used as model proteins. Based on TEM imaging and iSEC, the Nuvia resins have a microgranular structure and large pores (110 nm radius), while the Capto resins have a fibrous structure and smaller pores (32-36 nm radius). Comparable binding capacities (80-110 mg/mL), decreasing as salt is added, are observed for all three proteins on the Nuvia resins. Higher capacities (110-130 mg/mL), also decreasing as salt is added, are observed for BSA monomer and dimer on the Capto resins. However, the Tg binding capacity is very low in this case and increases as salt is added. Confocal laser scanning microscopy show that the kinetics are controlled by pore diffusion for all four resins, but with diffusivities that decrease as the protein size increases especially for the Capto resins. For Tg at low salt, binding is restricted to a thin shell close to the bead surface for both Capto resins. The ratio of effective and free diffusivity is about 0.30, 0.18, and 0.08 for BSA monomer, BSA dimer, and Tg, respectively, on the Nuvia resin. These values decrease to about 0.11, 0.04, and 0.01, respectively, for the Capto resins as a result of diffusional hindrance. Dynamic binding capacities are consistent with the equilibrium and rate behaviors.
Topics: Adsorption; Anion Exchange Resins; Anions; Chromatography, Ion Exchange; Diffusion; Hydrophobic and Hydrophilic Interactions; Kinetics; Ligands; Polymers; Proteins; Sepharose; Serum Albumin, Bovine
PubMed: 32822983
DOI: 10.1016/j.chroma.2020.461444