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Journal of Fluorescence May 2022In most biological processes, diffusion plays a critical role in transferring various bio-molecules to transfer desirable locations in an effective and energy-efficient...
In most biological processes, diffusion plays a critical role in transferring various bio-molecules to transfer desirable locations in an effective and energy-efficient manner. How fast molecules are transferred is measured by diffusion coefficients. Since each bio-molecules, in particular, signaling molecules have their unique diffusion coefficients and quantifying the diffusion coefficients help us to understand various time scales of both physiological and pathological processes in biological systems. Moreover, since diffusion profiles of a diffusant vary in different micro-environments of cell membranes, accurate diffusion coefficient also can provide a good picture of membrane landscapes as well as interactions of different membrane constituents. Currently, only a few experimental methods are available to assess the diffusion coefficient of a biomolecule of interest in live cells including Fluorescence Recovery After Photobleaching (FRAP). FRAP was developed to study diffusion processes of biomolecules in the cell membranes in the 1970s. Albeit its long history, the main principle of FRAP analysis has remained unchanged since its inception: fitting FRAP data to a theoretical diffusion model for the best fitting diffusion coefficient or using the relation between the half time of recovery and ROI size. In this study, we developed a flexible yet versatile confocal FRAP data analysis framework based on linear regression analysis which allows FRAP users to determine the diffusion from either single or multiple FRAP data points without data fitting. We also validated this approach for a series of fluorescently labeled soluble and membrane-bound proteins and lipids.
Topics: Cell Membrane; Diffusion; Fluorescence Recovery After Photobleaching; Membrane Proteins; Regression Analysis
PubMed: 35254627
DOI: 10.1007/s10895-022-02926-1 -
Physical Review Letters Nov 2022We investigate the dynamics of a single chiral active particle subject to an external torque due to the presence of a gravitational field. Our computer simulations...
We investigate the dynamics of a single chiral active particle subject to an external torque due to the presence of a gravitational field. Our computer simulations reveal an arbitrarily strong increase of the long-time diffusivity of the gravitactic agent when the external torque approaches the intrinsic angular drift. We provide analytic expressions for the mean-square displacement in terms of eigenfunctions and eigenvalues of the noisy-driven-pendulum problem. The pronounced maximum in the diffusivity is then rationalized by the vanishing of the lowest eigenvalues of the Fokker-Planck equation for the angular motion as the rotational diffusion decreases and the underlying classical bifurcation is approached. A simple harmonic-oscillator picture for the barrier-dominated motion provides a quantitative description for the onset of the resonance while its range of validity is determined by the crossover to a critical-fluctuation-dominated regime.
Topics: Diffusion; Computer Simulation; Motion
PubMed: 36493425
DOI: 10.1103/PhysRevLett.129.228003 -
Journal of the Royal Society, Interface Nov 2022Budding allows virus replication and macromolecular secretion in cells through the formation of a membrane protrusion (bud) that evolves into an envelope. The largest...
Budding allows virus replication and macromolecular secretion in cells through the formation of a membrane protrusion (bud) that evolves into an envelope. The largest energetic barrier to bud formation is membrane deflection and is trespassed primarily thanks to nucleocapsid-membrane adhesion. Transmembrane proteins (TPs), which later form the virus ligands, are the main promotors of adhesion and can accommodate membrane bending thanks to an induced spontaneous curvature. Adhesive TPs must diffuse across the membrane from remote regions to gather on the bud surface, thus, diffusivity controls the kinetics. This paper proposes a simple model to describe diffusion-mediated budding unravelling important size limitations and size-dependent kinetics. The predicted optimal virion radius, giving the fastest budding, is validated against experiments for coronavirus, HIV, flu and hepatitis. Assuming exponential replication of virions and hereditary size, the model can predict the size distribution of a virus population. This is verified against experiments for SARS-CoV-2. All the above comparisons rely on the premise that budding poses the tightest size constraint. This is true in most cases, as demonstrated in this paper, where the proposed model is extended to describe virus infection via receptor- and clathrin-mediated endocytosis, and via membrane fusion.
Topics: Humans; SARS-CoV-2; COVID-19; Virus Replication; Virion; Diffusion
PubMed: 36321373
DOI: 10.1098/rsif.2022.0525 -
Medical Physics May 2022The goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess...
OBJECTIVE
The goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess system bias and linearity in apparent diffusion coefficient (ADC) measurements.
METHOD
ADC measurements were performed for 40 kDa (K40) PVP of six concentrations (0%, 10%, 20%, 30%, 40%, and 50% by weight) at three temperatures (19.5°C, 22.5°C, and 26.4°C), with internal phantom temperature monitored by optical thermometer (±0.2°C). To achieve ADC measurement and fit accuracy of better than 0.5%, three orthogonal diffusion gradients were calibrated using known water diffusivity at 0°C and system gradient nonlinearity maps. Noise-floor fit bias was also controlled by limiting the maximum b-value used for ADC calculation of each sample. The ADC temperature dependence was modeled by Arrhenius functions of each PVP concentration. The concentration dependence was modeled by quadratic function for ADC normalized by the theoretical water diffusion values. Calibration coefficients were obtained from linear regression model fits.
RESULTS
Measured phantom ADC values increased with temperature and decreasing PVP concentration, [PVP]. The derived Arrhenius model parameters for [PVP] between 0% and 50%, are reported and can be used for K40 ADC temperature calibration with absolute ADC error within ±0.016 μm /ms. Arrhenius model fit parameters normalized to water value scaled with [PVP] between 10% and 40%, and proportional change in activation energy increased faster than collision frequency. ADC normalization by water diffusivity, D , from the Speedy-Angell relation accounted for the bulk of temperature dependence (±0.035 μm /ms) and yielded quadratic calibration for ADC /D = (12.5 ± 0.7) ·10 ·[PVP] - (23.2 ± 0.3)·10 ·[PVP]+1, nearly independent of PVP molecular weight and temperature.
CONCLUSION
The study provides ground-truth ADC values for K40 PVP solutions commonly used in diffusion phantoms for scanning at ambient room temperature. The described procedures and the reported calibration can be used for quality control and standardization of measured ADC values of PVP at different concentrations and temperatures.
Topics: Diffusion; Diffusion Magnetic Resonance Imaging; Phantoms, Imaging; Povidone; Temperature; Water
PubMed: 35184316
DOI: 10.1002/mp.15556 -
Biomedical Physics & Engineering Express Aug 2023. EDBreast gel is an alternative Fricke gel dosimeter, read by Magnetic Resonance Imaging, in which sucrose is added to lower diffusion effects. This paper aims at...
. EDBreast gel is an alternative Fricke gel dosimeter, read by Magnetic Resonance Imaging, in which sucrose is added to lower diffusion effects. This paper aims at determining the dosimetric characteristics of this dosimeter.. The characterization has been performed in high energy photon beams. The dose-response of the gel has been evaluated as well as its detection limit, its fading effects, the reproducibility of its response and its stability over time. Its energy and dose-rate dependence has been investigated, and the overall dose uncertainty budget established. Once characterized, the dosimetry method has been applied to a simple reference irradiation case in a 6 MV photon beam, with the measurement of the lateral dose profile of a 2 × 2 cmfield. The results have been compared with microDiamond measurements.. In addition to its low diffusivity, the gel presents a high sensitivity, no dose-rate dependence consideringTPR20-10values ranging from 0.66 to 0.79 and an energy response comparable to ionization chambers. However, its non-linear dose-response induces a high uncertainty on the measured dose (8 % (k=1) at 20 Gy) and reproducibility issues. The profile measurements displayed discrepancies compared to the microDiamond due to diffusion effects. The appropriate spatial resolution was estimated using the diffusion coefficient.. EDBreast gel dosimeter presents interesting characteristics for applications in clinics, but the linearity of its dose-response should be improved to lower the uncertainties and to enhance the reproducibility.
Topics: Reproducibility of Results; Radiometry; Diffusion; Radiation Dosimeters; Uncertainty
PubMed: 37236157
DOI: 10.1088/2057-1976/acd942 -
Magnetic Resonance in Medical Sciences... Apr 2024Diffusion MRI is a physical measurement method that quantitatively indicates the displacement of water molecules diffusing in voxels. However, there are insufficient...
PURPOSE
Diffusion MRI is a physical measurement method that quantitatively indicates the displacement of water molecules diffusing in voxels. However, there are insufficient data to characterize the diffusion process physically in a uniform structure such as a phantom. This study investigated the transitional relationship between structure scale, temperature, and diffusion time for simple restricted diffusion using a capillary phantom.
METHODS
We performed diffusion-weighted pulsed-gradient stimulated-echo acquisition mode (STEAM) MRI with a 9.4 Tesla MRI system (Bruker BioSpin, Ettlingen, Germany) and a quadrature coil with an inner diameter of 86 mm (Bruker BioSpin). We measured the diffusion coefficients (radial diffusivity [RD]) of capillary plates (pore sizes 6, 12, 25, 50, and 100 μm) with uniformly restricted structures at various temperatures (10ºC, 20ºC, 30ºC, and 40ºC) and multiple diffusion times (12-800 ms). We evaluated the characteristics of scale, temperature, and diffusion time for restricted diffusion.
RESULTS
The RD decayed and became constant depending on the structural scale. Diffusion coefficient fluctuations with temperature occurred mostly under conditions of a large structural scale and short diffusion time. We obtained data suggesting that temperature-dependent changes in the diffusion coefficients follow physical laws.
CONCLUSION
No water molecules were observed outside the glass tubes in the capillary plates, and the capillary plates only reflected a restricted diffusion process within the structure.We experimentally evaluated the characteristics of simple restricted diffusion to reveal the transitional relationship of the diffusion coefficient with diffusion time, structure scale, and temperature through composite measurement.
Topics: Temperature; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging; Diffusion; Biological Transport; Phantoms, Imaging; Water
PubMed: 36754420
DOI: 10.2463/mrms.mp.2022-0103 -
Journal of Chemical Theory and... Jun 2022Modeling of diffusion of adsorbates through porous materials with atomistic molecular dynamics (MD) can be a challenging task if the flexibility of the adsorbent needs...
Modeling of diffusion of adsorbates through porous materials with atomistic molecular dynamics (MD) can be a challenging task if the flexibility of the adsorbent needs to be included. This is because potentials need to be developed that accurately account for the motion of the adsorbent in response to the presence of adsorbate molecules. In this work, we show that it is possible to use accurate machine learning atomistic potentials for metal-organic frameworks in concert with classical potentials for adsorbates to accurately compute diffusivities though a hybrid potential approach. As a proof-of-concept, we have developed an accurate deep learning potential (DP) for UiO-66, a metal-organic framework, and used this DP to perform hybrid potential simulations, modeling diffusion of neon and xenon through the crystal. The adsorbate-adsorbate interactions were modeled with Lennard-Jones (LJ) potentials, the adsorbent-adsorbent interactions were described by the DP, and the adsorbent-adsorbate interactions used LJ cross-interactions. Thus, our hybrid potential allows for adsorbent-adsorbate interactions with classical potentials but models the response of the adsorbent to the presence of the adsorbate through near-DFT accuracy DPs. This hybrid approach does not require refitting the DP for new adsorbates. We calculated self-diffusion coefficients for Ne in UiO-66 from DFT-MD, our hybrid DP/LJ approach, and from two different classical potentials for UiO-66. Our DP/LJ results are in excellent agreement with DFT-MD. We modeled diffusion of Xe in UiO-66 with DP/LJ and a classical potential. Diffusion of Xe in UiO-66 is about a factor of 30 slower than that of Ne, so it is not computationally feasible to compute Xe diffusion with DFT-MD. Our hybrid DP-classical potential approach can be applied to other MOFs and other adsorbates, making it possible to use an accurate DP generated from DFT simulations of an empty adsorbent in concert with existing classical potentials for adsorbates to model adsorption and diffusion within the porous material, including adsorbate-induced changes to the framework.
Topics: Adsorption; Deep Learning; Diffusion; Metal-Organic Frameworks; Phthalic Acids
PubMed: 35653218
DOI: 10.1021/acs.jctc.2c00010 -
Comparative Biochemistry and... Mar 2021The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ,... (Review)
Review
The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ, by mass, skeletal muscle contains a prodigious surface area of capillaries that have a critical role in metabolic homeostasis and must support energetic requirements that increase as much as 100-fold from rest to maximal exercise. In 1919 Krogh's 3 papers, published in the Journal of Physiology, brilliantly conflated measurements of muscle capillary function at rest and during contractions with Agner K. Erlang's mathematical model of O diffusion. These papers single-handedly changed the perception of capillaries from passive vessels serving at the mercy of their upstream arterioles into actively contracting vessels that were recruited during exercise to elevate blood-myocyte O flux. Although seminal features of Krogh's model have not withstood the test of time and subsequent technological developments, Krogh is credited with helping found the field of muscle microcirculation and appreciating the role of the capillary bed and muscle O diffusing capacity in facilitating blood-myocyte O flux. Today, thanks in large part to Krogh, it is recognized that comprehending the role of the microcirculation, as it supports perfusive and diffusive O conductances, is fundamental to understanding skeletal muscle plasticity with exercise training and resolving the mechanistic bases by which major pathologies including heart failure and diabetes cripple exercise tolerance and cerebrovascular dysfunction predicates impaired executive function.
Topics: Animals; Capillaries; Diffusion; Humans; Muscle Cells; Muscles; Oxygen
PubMed: 33242636
DOI: 10.1016/j.cbpa.2020.110852 -
NeuroImage Oct 2023Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background...
Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background connectivity between the pulvinar and V1 in relation to focused versus diffused attention allocation, in weak and strong crowding contexts. Our findings revealed that focused attention led to enhanced correlations between the pulvinar and V1. Notably, this modulation was initiated by the pulvinar, and the strength of the modulation was dependent on the saliency of the target. These findings suggest that the pulvinar initiates information reweighting to V1, which underlies attentional selection in cluttered scenes.
Topics: Humans; Pulvinar; Cognition; Diffusion
PubMed: 37619793
DOI: 10.1016/j.neuroimage.2023.120341 -
Biomaterials Oct 2023Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells... (Review)
Review
Flourished in the past two decades, fluorescent probe technology provides researchers with accurate and efficient tools for in situ imaging of biomarkers in living cells and tissues and may play a significant role in clinical diagnosis and treatment such as biomarker detection, fluorescence imaging-guided surgery, and photothermal/photodynamic therapy. In situ imaging of biomarkers depends on the spatial resolution of molecular probes. Nevertheless, the majority of currently available molecular fluorescent probes suffer from the drawback of diffusing from the target region. This leads to a rapid attenuation of the fluorescent signal over time and a reduction in spatial resolution. Consequently, the diffused fluorescent signal cannot accurately reflect the in situ information of the target. Self-immobilizing and self-precipitating molecular fluorescent probes can be used to overcome this problem. These probes ensure that the fluorescent signal remains at the location where the signal is generated for a long time. In this review, we introduce the development history of the two types of probes and classify them in detail according to different design strategies. In addition, we compare their advantages and disadvantages, summarize some representative studies conducted in recent years, and propose prospects for this field.
Topics: Fluorescent Dyes; Molecular Probes; Diagnostic Imaging; Diffusion; Photothermal Therapy
PubMed: 37643487
DOI: 10.1016/j.biomaterials.2023.122281