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Scientific Reports Jun 2022In this paper we present random walk based solutions to diffusion in semi-permeable layered media with varying diffusivity. We propose a novel transit model for solving...
In this paper we present random walk based solutions to diffusion in semi-permeable layered media with varying diffusivity. We propose a novel transit model for solving the interaction of random walkers with a membrane. This hybrid model is based on treating the membrane permeability and the step change in diffusion coefficient as two interactions separated by an infinitesimally small layer. By conducting an extensive analytical flux analysis, the performance of our hybrid model is compared with a commonly used membrane transit model (reference model). Numerical simulations demonstrate the limitations of the reference model in dealing with step changes in diffusivity and show the capability of the hybrid model to overcome this limitation and to offer substantial gains in computational efficiency. The suitability of both random walk transit models for the application to simulations of diffusion tensor cardiovascular magnetic resonance (DT-CMR) imaging is assessed in a histology-based domain relevant to DT-CMR. In order to demonstrate the usefulness of the new hybrid model for other possible applications, we also consider a larger range of permeabilities beyond those commonly found in biological tissues.
Topics: Diffusion; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Heart; Magnetic Resonance Imaging
PubMed: 35750717
DOI: 10.1038/s41598-022-14541-y -
The Journal of Biological Chemistry Aug 2019Cholesterol constitutes ∼30-40% of the mammalian plasma membrane, a larger fraction than of any other single component. It is a major player in numerous signaling...
Cholesterol constitutes ∼30-40% of the mammalian plasma membrane, a larger fraction than of any other single component. It is a major player in numerous signaling processes as well as in shaping molecular membrane architecture. However, our knowledge of the dynamics of cholesterol in the plasma membrane is limited, restricting our understanding of the mechanisms regulating its involvement in cell signaling. Here, we applied advanced fluorescence imaging and spectroscopy approaches on (model membranes) and (live cells and embryos) membranes as well as analysis to systematically study the nanoscale dynamics of cholesterol in biological membranes. Our results indicate that cholesterol diffuses faster than phospholipids in live membranes, but not in model membranes. Interestingly, a detailed statistical diffusion analysis suggested two-component diffusion for cholesterol in the plasma membrane of live cells. One of these components was similar to a freely diffusing phospholipid analogue, whereas the other one was significantly faster. When a cholesterol analogue was localized to the outer leaflet only, the fast diffusion of cholesterol disappeared, and it diffused similarly to phospholipids. Overall, our results suggest that cholesterol diffusion in the cell membrane is heterogeneous and that this diffusional heterogeneity is due to cholesterol's nanoscale interactions and localization in the membrane.
Topics: Animals; CHO Cells; Cell Membrane; Cells, Cultured; Cholesterol; Cricetulus; Diffusion; Female; Male; Molecular Dynamics Simulation; Monte Carlo Method; Nanotechnology; Spectrometry, Fluorescence; Zebrafish
PubMed: 31270209
DOI: 10.1074/jbc.RA119.009683 -
International Journal of Pharmaceutics Oct 2021The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics...
The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (R) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent - glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF's permeation, whilst HC permeability is a partition-driven process.
Topics: Comprehension; Diffusion; Hydrophobic and Hydrophilic Interactions; Intestinal Absorption; Permeability; Pharmaceutical Preparations
PubMed: 34555476
DOI: 10.1016/j.ijpharm.2021.121116 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2015To compare the diffusion properties of fluorescent probes dextran-tetramethylrhodamine (DT) and lucifer yellow CH (LY) and magnetic probe gadolinium-diethylene triamine...
OBJECTIVE
To compare the diffusion properties of fluorescent probes dextran-tetramethylrhodamine (DT) and lucifer yellow CH (LY) and magnetic probe gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in porous media and to screen out a suitable fluorescent probe for optical imaging of brain interstitial space (ISS).
METHODS
Agarose gels sample were divided into DT group, LY group and Gd-DTPA group, and the corresponding molecular probes were imported in each group. The dynamic diffusions of DT and LY in agarose gels at different time points (15, 30, 45, 60, 90, and 120 min) were scanned with laser scanning confocal microscope, the dynamic diffusion of Gd-DTPA was imaged with magnetic resonance imaging. The average diffusion speed of LY were demonstrated to be consistent with those of Gd-DTPA. The LY was introduced into caudate putamen of 18 rats, respectively, the diffusion of LY in the sequential slices of rat brain at different time points (0.5, 1, 2, 3, 7, 11 h) were scanned, and the results were compared with those of rats' brain with Gd-DTPA imported and imaged in vivo with magnetic resonance imaging.
RESULTS
The diffusions of the three probes were isotropic in the agarose gels, and the average diffusion speeds of DT, LY and Gd-DTPA were: (0.07±0.02)×10(-2) mm2/s, (1.54±0.47)×10(-2) mm2/s, (1.45±0.50)×10(-2) mm2/s, respectively. The speed of DT was more slower than both LY and Gd-DTPA (ANOVA, F=367.15, P<0.001; Post-Hoc LSD, P<0.001), and there was no significant difference between the speeds of LY and Gd-DTPA (Post-Hoc LSD, P=0.091). The variation tendency of diffusion area of DT was different with both that of LY and that of Gd-DTPA (Bonferroni correction, α=0.0125, P<0.001), and there was no significant difference between LY and Gd-DTPA (Bonferroni correction, α=0.0125, P=0.203), in analysis by repeated measures data of ANOVA. The diffusions of LY and Gd-DTPA were anisotropy in rat caudate putamen,and the average diffusion speeds of LY and Gd-DTPA were: (1.03±0.29)×10(-3) mm2/s, (0.81±0.27)×10(-3) mm2/s, respectively, no significant difference was demonstrated (t=0.759, P=0.490); half-time of single intensity of LY and Gd-DTPA was (2.58±0.04) h, (2.46±0.10) h, respectively, no significant difference was found (t=2.025, P=0.113). The diffusion area ratios between LY and Gd-DTPA in rat caudate putamen was not statistically different at hours 0.5, 1, 2, 3 and 7 (t=2.249, P=0.088; t=2.582, P=0.061; t=1.966, P=0.121; t=0.132, P=0.674; t=0.032, P=0.976), while, a slightly difference was found at 11 h (t=2.917, P=0.043,in analysis by t test).
CONCLUSION
LY present the same diffusion property with Gd-DTPA in porous media witch including agarose gels and live rat brain tissue, indicates that LY is a suitable fluorescent probe for optical imaging of brain ISS, and it can be used for microscopic, macro and in vitro measure of brain ISS.
Topics: Animals; Brain; Contrast Media; Diffusion; Fluorescence; Fluorescent Dyes; Gadolinium DTPA; Magnetic Resonance Imaging; Microscopy, Confocal; Molecular Probes; Neuroimaging; Rats
PubMed: 26284407
DOI: No ID Found -
Biophysical Journal Apr 2021In obstacle-filled media, such as extracellular or intracellular lumen of brain tissue, effective ion-diffusion permeability is a key determinant of electrogenic...
In obstacle-filled media, such as extracellular or intracellular lumen of brain tissue, effective ion-diffusion permeability is a key determinant of electrogenic reactions. Although this diffusion permeability is thought to depend entirely on structural features of the medium, such as porosity and tortuosity, brain tissue shows prominent nonohmic properties, the origins of which remain poorly understood. Here, we explore Monte Carlo simulations of ion diffusion in a space filled with overlapping spheres to predict that diffusion permeability of such media decreases with stronger external electric fields. This dependence increases with lower medium porosity while decreasing with radial (two-dimensional or three-dimensional) compared with homogenous (one-dimensional) fields. We test our predictions empirically in an electrolyte chamber filled with microscopic glass spheres and find good correspondence with our predictions. A theoretical insight relates this phenomenon to a disproportionately increased dwell time of diffusing ions at potential barriers (or traps) representing geometric obstacles when the field strength increases. The dependence of medium ion-diffusion permeability on electric field could be important for understanding conductivity properties of porous materials, in particular for the accurate interpretation of electric activity recordings in brain tissue.
Topics: Diffusion; Electric Conductivity; Monte Carlo Method; Permeability; Porosity
PubMed: 33609495
DOI: 10.1016/j.bpj.2021.02.012 -
Biophysical Journal May 2019The trajectory of a single protein in the cytosol of a living cell contains information about its molecular interactions in its native environment. However, it has...
The trajectory of a single protein in the cytosol of a living cell contains information about its molecular interactions in its native environment. However, it has remained challenging to accurately resolve and characterize the diffusive states that can manifest in the cytosol using analytical approaches based on simplifying assumptions. Here, we show that multiple intracellular diffusive states can be successfully resolved if sufficient single-molecule trajectory information is available to generate well-sampled distributions of experimental measurements and if experimental biases are taken into account during data analysis. To address the inherent experimental biases in camera-based and MINFLUX-based single-molecule tracking, we use an empirical data analysis framework based on Monte Carlo simulations of confined Brownian motion. This framework is general and adaptable to arbitrary cell geometries and data acquisition parameters employed in two-dimensional or three-dimensional single-molecule tracking. We show that, in addition to determining the diffusion coefficients and populations of prevalent diffusive states, the timescales of diffusive state switching can be determined by stepwise increasing the time window of averaging over subsequent single-molecule displacements. Time-averaged diffusion analysis of single-molecule tracking data may thus provide quantitative insights into binding and unbinding reactions among rapidly diffusing molecules that are integral for cellular functions.
Topics: Computer Simulation; Cytoplasm; Cytosol; Diffusion; Kinetics; Monte Carlo Method; Single Molecule Imaging; Time Factors
PubMed: 31030884
DOI: 10.1016/j.bpj.2019.03.039 -
Computers in Biology and Medicine Sep 2022We develop a lumped parameter model to describe and predict the mass release of (absorption from) an arbitrary shaped body of any dimension in a large environment....
We develop a lumped parameter model to describe and predict the mass release of (absorption from) an arbitrary shaped body of any dimension in a large environment. Through the one-to-one analogy between diffusion-dominated mass transfer systems and electrical circuits we provide exact solutions in terms of averaged concentrations and mass released. An estimate of the equivalent resistance and of the release time is also given, and shown to be inversely proportional to the diffusivity. The proposed electrical analogue approach allows a time constant to be defined and provides an easy extension to a multi-layer and multi-phase cases in planar and spherical geometries. The simulation results are compared with those obtained from the solution of the corresponding analytical, numerical and experimental solutions, showing a satisfactory accuracy and a good agreement.
Topics: Computer Simulation; Diffusion; Electricity; Mathematics
PubMed: 35834969
DOI: 10.1016/j.compbiomed.2022.105774 -
NeuroImage Feb 2017Inferring the microstructure of complex media from the diffusive motion of molecules is a challenging problem in diffusion physics. In this paper, we introduce a novel...
Inferring the microstructure of complex media from the diffusive motion of molecules is a challenging problem in diffusion physics. In this paper, we introduce a novel representation of diffusion MRI (dMRI) signal from tissue with spatially-varying diffusivity using a diffusion disturbance function. This disturbance function contains information about the (intra-voxel) spatial fluctuations in diffusivity due to restrictions, hindrances and tissue heterogeneity of the underlying tissue substrate. We derive the short- and long-range disturbance coefficients from this disturbance function to characterize the tissue structure and organization. Moreover, we provide an exact relation between the disturbance coefficients and the time-varying moments of the diffusion propagator, as well as their relation to specific tissue microstructural information such as the intra-axonal volume fraction and the apparent axon radius. The proposed approach is quite general and can model dMRI signal for any type of gradient sequence (rectangular, oscillating, etc.) without using the Gaussian phase approximation. The relevance of the proposed PICASO model is explored using Monte-Carlo simulations and in-vivo dMRI data. The results show that the estimated disturbance coefficients can distinguish different types of microstructural organization of axons.
Topics: Axons; Brain; Brain Mapping; Diffusion; Diffusion Magnetic Resonance Imaging; Humans; Image Processing, Computer-Assisted
PubMed: 27751940
DOI: 10.1016/j.neuroimage.2016.09.057 -
ACS Nano Jan 2021The permeability of hydrogels for the selective transport of molecular penetrants (drugs, toxins, reactants, .) is a central property in the design of soft functional...
The permeability of hydrogels for the selective transport of molecular penetrants (drugs, toxins, reactants, .) is a central property in the design of soft functional materials, for instance in biomedical, pharmaceutical, and nanocatalysis applications. However, the permeation of dense and hydrated polymer membranes is a complex multifaceted molecular-level phenomenon, and our understanding of the underlying physicochemical principles is still very limited. Here, we uncover the molecular principles of permeability and selectivity in hydrogel permeation. We combine the solution-diffusion model for permeability with comprehensive atomistic simulations of molecules of various shapes and polarities in a responsive hydrogel in different hydration states. We find in particular that dense collapsed states are extremely selective, owing to a delicate balance between the partitioning and diffusivity of the penetrants. These properties are sensitively tuned by the penetrant size, shape, and chemistry, leading to vast cancellation effects, which nontrivially contribute to the permeability. The gained insights enable us to formulate semiempirical rules to quantify and extrapolate the permeability categorized by classes of molecules. They can be used as approximate guiding ("rule-of-thumb") principles to optimize penetrant or membrane physicochemical properties for a desired permeability and membrane functionality.
Topics: Diffusion; Hydrogels; Permeability; Polymers
PubMed: 33382598
DOI: 10.1021/acsnano.0c06319 -
Angewandte Chemie (International Ed. in... Mar 2022Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like... (Review)
Review
Numerous key biological processes rely on the concept of multivalency, where ligands achieve stable binding only upon engaging multiple receptors. These processes, like viral entry or immune synapse formation, occur on the diffusive cellular membrane. One crucial, yet underexplored aspect of multivalent binding is the mobility of coupled receptors. Here, we discuss the consequences of mobility in multivalent processes from four perspectives: (I) The facilitation of receptor recruitment by the multivalent ligand due to their diffusivity prior to binding. (II) The effects of receptor preassembly, which allows their local accumulation. (III) The consequences of changes in mobility upon the formation of receptor/ligand complex. (IV) The changes in the diffusivity of lipid environment surrounding engaged receptors. We demonstrate how understanding mobility is essential for fully unravelling the principles of multivalent membrane processes, leading to further development in studies on receptor interactions, and guide the design of new generations of multivalent ligands.
Topics: Cell Membrane; Diffusion; Ligands; Lipids
PubMed: 34982497
DOI: 10.1002/anie.202114167