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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 -
Soft Matter Oct 2023The lateral diffusion of cell membrane inclusions, such as integral membrane proteins and bound receptors, drives critical biological processes, including the formation...
The lateral diffusion of cell membrane inclusions, such as integral membrane proteins and bound receptors, drives critical biological processes, including the formation of complexes, cell-cell signaling, and membrane trafficking. These diffusive processes are complicated by how concentrated, or "crowded", the inclusions are, which can occupy between 30-50% of the area fraction of the membrane. In this work, we elucidate the effects of increasing concentration of model membrane inclusions in a free-standing artificial cell membrane on inclusion diffusivity and the apparent viscosity of the membrane. By multiple particle tracking of fluorescent microparticles covalently tethered to the bilayer, we show the transition from expected Brownian dynamics, which accurately measure the membrane viscosity, to subdiffusive behavior with decreased diffusion coefficient as the particle area fraction increases from 1% to around 30%, approaching physiological levels of crowding. At high crowding, the onset of non-Gaussian behavior is observed. Using hydrodynamic models relating the 2D diffusion coefficient to the viscosity of a membrane, we determine the apparent viscosity of the bilayer from the particle diffusivity and show an increase in the apparent membrane viscosity with increasing particle area fraction. However, the scaling of this increase is in contrast with the behavior of monolayer inclusion diffusion and bulk suspension rheology. These results demonstrate that physiological levels of model membrane crowding nontrivially alter the dynamics and apparent viscosity of the system, which has implications for understanding membrane protein interactions and particle-membrane transport processes.
Topics: Membranes; Membrane Proteins; Molecular Dynamics Simulation; Biophysical Phenomena; Diffusion; Membranes, Artificial; Viscosity
PubMed: 37791427
DOI: 10.1039/d3sm01269g -
Single-molecule displacement mapping unveils nanoscale heterogeneities in intracellular diffusivity.Nature Methods May 2020Intracellular diffusion underlies vital cellular processes. However, it remains difficult to elucidate how an unbound protein diffuses inside the cell with good spatial...
Intracellular diffusion underlies vital cellular processes. However, it remains difficult to elucidate how an unbound protein diffuses inside the cell with good spatial resolution and sensitivity. Here we introduce single-molecule displacement/diffusivity mapping (SMdM), a super-resolution strategy that enables the nanoscale mapping of intracellular diffusivity through local statistics of the instantaneous displacements of freely diffusing single molecules. We thus show that the diffusion of an average-sized protein in the mammalian cytoplasm and nucleus is spatially heterogeneous at the nanoscale, and that variations in local diffusivity correlate with the ultrastructure of the actin cytoskeleton and the organization of the genome, respectively. SMdM of differently charged proteins further unveils that the possession of positive, but not negative, net charges drastically impedes diffusion, and that the rate is determined by the specific subcellular environments. We thus unveil rich heterogeneities and charge effects in intracellular diffusion at the nanoscale.
Topics: Cell Nucleus; Cells, Cultured; Cytoplasm; Diffusion; Humans; Image Interpretation, Computer-Assisted; Intracellular Space; Microscopy, Fluorescence; Models, Theoretical; Nanoparticles; Proteins; Single Molecule Imaging
PubMed: 32203387
DOI: 10.1038/s41592-020-0793-0 -
Journal of Biomechanical Engineering Nov 2022Due to lack of full vascularization, the meniscus relies on diffusion through the extracellular matrix to deliver small (e.g., nutrients) and large (e.g., proteins) to...
Due to lack of full vascularization, the meniscus relies on diffusion through the extracellular matrix to deliver small (e.g., nutrients) and large (e.g., proteins) to resident cells. Under normal physiological conditions, the meniscus undergoes up to 20% compressive strains. While previous studies characterized solute diffusivity in the uncompressed meniscus, to date, little is known about the diffusive transport under physiological strain levels. This information is crucial to fully understand the pathophysiology of the meniscus. The objective of this study was to investigate strain-dependent diffusive properties of the meniscus fibrocartilage. Tissue samples were harvested from the central portion of porcine medial menisci and tested via fluorescence recovery after photobleaching to measure diffusivity of fluorescein (332 Da) and 40 K Da dextran (D40K) under 0%, 10%, and 20% compressive strain. Specifically, average diffusion coefficient and anisotropic ratio, defined as the ratio of the diffusion coefficient in the direction of the tissue collagen fibers to that orthogonal, were determined. For all the experimental conditions investigated, fluorescein diffusivity was statistically faster than that of D40K. Also, for both molecules, diffusion coefficients significantly decreased, up to ∼45%, as the strain increased. In contrast, the anisotropic ratios of both molecules were similar and not affected by the strain applied to the tissue. This suggests that compressive strains used in this study did not alter the diffusive pathways in the meniscus. Our findings provide new knowledge on the transport properties of the meniscus fibrocartilage that can be leveraged to further understand tissue pathophysiology and approaches to tissue restoration.
Topics: Animals; Anisotropy; Diffusion; Fibrocartilage; Fluoresceins; Meniscus; Swine
PubMed: 35789377
DOI: 10.1115/1.4054931 -
Physica Medica : PM : An International... Nov 2022The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient...
PURPOSE
The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient (ADC) and other radiomic features across the scanners involved in the REGINA trial.
MATERIALS AND METHODS
The NIST/QIBA diffusion phantom was acquired on six 3 T scanners from five centres with a rectum-specific diffusion protocol. All sequences were repeated in each scan session without moving the phantom from the table. Linear interpolation to two isotropic voxel spacing (0.9 and 4 mm) was performed as well as the ComBat feature harmonisation method between scanners. The absolute accuracy error was evaluated for the mean ADC. Repeatability and reproducibility within-subject coefficients of variation (wCV) were computed for 142 radiomic features.
RESULTS
For the mean ADC, accuracy error ranged between 0.1 % and 8.5 %, repeatability was <1 % and reproducibility was <3 % for diffusivity range between 0.4 and 1.1x10mm/s. For the other radiomic features, wCV was below 10 % for 24 % and 15 % features for repeatability with resampling 0.9 mm and 4 mm, respectively, and 13 % and 11 % feature for reproducibility. ComBat method could improve significantly the wCV compared to reproducibility without ComBat (p-value < 0.001) but variation was still high for most of the features.
CONCLUSION
Our study provided the first investigation of feature selection for development of robust predictive models in the REGINA trial, demonstrating the added value of such a quality assurance process to select conventional and radiomic features in prospective multicentre trials.
Topics: Reproducibility of Results; Prospective Studies; Diffusion Magnetic Resonance Imaging; Phantoms, Imaging; Diffusion
PubMed: 36308999
DOI: 10.1016/j.ejmp.2022.10.009 -
Journal of the Royal Society, Interface Mar 2021A recent experiment (Sadoon AA, Wang Y. 2018 , 042411. (doi:10.1103/PhysRevE.98.042411)) has revealed that nucleoid-associated proteins (i.e. DNA-binding proteins)...
A recent experiment (Sadoon AA, Wang Y. 2018 , 042411. (doi:10.1103/PhysRevE.98.042411)) has revealed that nucleoid-associated proteins (i.e. DNA-binding proteins) exhibit highly heterogeneous diffusion processes in bacteria where not only the diffusion constant but also the anomalous diffusion exponent fluctuates for the various proteins. The distribution of displacements of such proteins is observed to take a -Gaussian form, which decays as a power law. Here, a statistical model is developed for the diffusive motion of the proteins within the bacterium, based on a superstatistics with two variables. This model hierarchically takes into account the joint fluctuations of both the anomalous diffusion exponents and the diffusion constants. A fractional Brownian motion is discussed as a possible local model. Good agreement with the experimental data is obtained.
Topics: Bacteria; Bacterial Proteins; Diffusion; Models, Statistical; Motion
PubMed: 33653112
DOI: 10.1098/rsif.2020.0927 -
Journal of the Mechanical Behavior of... Jan 2024Hydrogels are a promising class of material in biomedical and industrial applications, where both the mechanical and diffusion properties play an important role. The...
Hydrogels are a promising class of material in biomedical and industrial applications, where both the mechanical and diffusion properties play an important role. The wide range of polymers that can be used and the different production methods allows these properties to be specifically tuned to a high degree for their application. Producing tough hydrogels with high stiffness has been a long-standing challenge that has recently been addressed by mineralisation methods. Those methods modify the hydrogel into one with a supporting mineral microstructure that is highly heterogeneous. This work investigates methods to determine the macroscopic diffusion behaviour of heterogeneous gels by a homogenisation method implemented in a finite element framework. This is applied to two recently developed materials by calcifying poly-dimethyl-acrylamide (PDMA) and polyacrylamide hydrogels (PAAm). The former has porous, spherical inclusions obstructing diffusion, while the latter has spherical pores enabling it. For both gels the unobstructed volume can be used as the primary parameter to tune the diffusivity. In PDMA the porosity of the obstructions is shown by multiscale analysis to give a strong, non-linear dependence of the diffusivity on the solute molecule radius. The framework is extended to other materials and comparisons are made to experimental works from the literature.
Topics: Hydrogels; Polymers; Calcification, Physiologic; Porosity; Diffusion
PubMed: 37988844
DOI: 10.1016/j.jmbbm.2023.106244 -
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 -
International Journal of Pharmaceutics Jan 2023Warming the skin is a key means of promoting solute permeation through the skin. Changes in solute permeation associated with variations in skin temperature also assist...
Warming the skin is a key means of promoting solute permeation through the skin. Changes in solute permeation associated with variations in skin temperature also assist in understanding the mechanism by which solutes permeate the skin. However, few studies have considered the relative impact of temperature on the main determinants of the maximum flux for a solute across the skin, the solubility of a solute and its diffusivity in the stratum corneum. In this study, we quantified for the first time the thermodynamics associated with the maximum skin fluxes for a series of phenolic compounds of similar size but with varying lipophilicity (defined by the logarithms of their octanol/water partition coefficient, logP). These studies were undertaken using aqueous donor solutions (along with testosterone as a reference solute) across human epidermal membranes in vertical Franz diffusion cells at 4 °C, 24 °C and 37 °C with intermittent receptor sampling and volume replacement over 24 h. Kinetic and thermodynamic analyses included the estimation of the stratum corneum (SC) apparent SC diffusivity from the SC maximum fluxes and SC solubilities and the associated activation energies, enthalpies and entropies for diffusion. The key findings were that the differences in the maximum flux of phenolic compounds varying in lipophilicity mainly arose from differences in SC solubility at the various temperatures and that, at the highest temperature, SC permeability and SC diffusion were affected by SC lipid fluidisation and that variations in SC - water partitioning enthalpies explain some of the previously low activation energies for permeation of the more lipophilic phenols. Higher enthalpies for diffusion were seen for solutes with addition hydrogen bonding capacity and the highest negative entropy was observed with the more compact solutes. Various relationships between the derived thermodynamic parameters were explored and interpreted in a proposed model for solute partitioning into and permeation through the SC intercellular lipid lamellae.
Topics: Humans; Skin Absorption; Kinetics; Diffusion; Permeability; Phenols; Solutions; Thermodynamics; Water; Lipids
PubMed: 36563793
DOI: 10.1016/j.ijpharm.2022.122522 -
Proceedings of the National Academy of... Sep 2022Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show...
Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show that the shrinking and swelling kinetics of self-healing hydrogels could be intrinsically asymmetric. The structure frustration, formed by the large difference in the heat and solvent diffusions, remarkably slows down the shrinking kinetics. The plateau modulus of viscoelastic gels is found to be a key parameter governing the formation of structure frustration and, in turn, the asymmetric swelling and shrinking kinetics. This work provides fundamental understandings on the temperature-triggered transient structure formation in self-healing hydrogels. Our findings will find broad use in diverse applications of self-healing hydrogels, where cooperative diffusion of water and gel network is involved. Our findings should also give insight into the molecular diffusion in biological systems that possess macromolecular crowding environments similar to self-healing hydrogels.
Topics: Diffusion; Hydrogels; Kinetics; Temperature; Water
PubMed: 36037384
DOI: 10.1073/pnas.2207422119