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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 -
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 -
Journal of the Science of Food and... May 2015The mass transfer parameters diffusion and sorption in food and packaging or between them are the key parameters for assessing a food product's shelf-life in reference... (Review)
Review
The mass transfer parameters diffusion and sorption in food and packaging or between them are the key parameters for assessing a food product's shelf-life in reference to consumer safety. This has become of paramount importance owing to the legislations set by the regulated markets. The technical capabilities that can be exploited for analyzing product-package interactions have been growing rapidly. Different techniques categorized according to the state of the diffusant (gas or liquid) in contact with the packaging material are emphasized in this review. Depending on the diffusant and on the analytical question under review, the different ways to study sorption and/or migration are presented and compared. Some examples have been suggested to reach the best possible choice, consisting of a single technique or a combination of different approaches.
Topics: Adsorption; Diffusion; Food Contamination; Food Packaging; Humans; Molecular Weight; Plastics
PubMed: 25123587
DOI: 10.1002/jsfa.6872 -
Journal of Mathematical Biology Mar 2015By introducing linear cross-diffusion for a two-component reaction-diffusion system with activator-depleted reaction kinetics (Gierer and Meinhardt, Kybernetik 12:30-39,...
By introducing linear cross-diffusion for a two-component reaction-diffusion system with activator-depleted reaction kinetics (Gierer and Meinhardt, Kybernetik 12:30-39, 1972; Prigogine and Lefever, J Chem Phys 48:1695-1700, 1968; Schnakenberg, J Theor Biol 81:389-400, 1979), we derive cross-diffusion-driven instability conditions and show that they are a generalisation of the classical diffusion-driven instability conditions in the absence of cross-diffusion. Our most revealing result is that, in contrast to the classical reaction-diffusion systems without cross-diffusion, it is no longer necessary to enforce that one of the species diffuse much faster than the other. Furthermore, it is no longer necessary to have an activator-inhibitor mechanism as premises for pattern formation, activator-activator, inhibitor-inhibitor reaction kinetics as well as short-range inhibition and long-range activation all have the potential of giving rise to cross-diffusion-driven instability. To support our theoretical findings, we compute cross-diffusion induced parameter spaces and demonstrate similarities and differences to those obtained using standard reaction-diffusion theory. Finite element numerical simulations on planary square domains are presented to back-up theoretical predictions. For the numerical simulations presented, we choose parameter values from and outside the classical Turing diffusively-driven instability space; outside, these are chosen to belong to cross-diffusively-driven instability parameter spaces. Our numerical experiments validate our theoretical predictions that parameter spaces induced by cross-diffusion in both the [Formula: see text] and [Formula: see text] components of the reaction-diffusion system are substantially larger and different from those without cross-diffusion. Furthermore, the parameter spaces without cross-diffusion are sub-spaces of the cross-diffusion induced parameter spaces. Our results allow experimentalists to have a wider range of parameter spaces from which to select reaction kinetic parameter values that will give rise to spatial patterning in the presence of cross-diffusion.
Topics: Biological Transport, Active; Computer Simulation; Diffusion; Finite Element Analysis; Kinetics; Linear Models; Mathematical Concepts; Models, Biological
PubMed: 24671430
DOI: 10.1007/s00285-014-0779-6 -
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 -
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 -
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 -
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 -
ACS Biomaterials Science & Engineering Sep 2021Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These -like 3D environments...
Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These -like 3D environments provide a basis for tissue engineering and cell therapies but also for research into fundamental biological questions and disease modeling. The physical properties of PEG hydrogels can be modulated to provide mechanical cues to encapsulated cells; however, the impact of changing hydrogel stiffness on the diffusivity of solutes to and from encapsulated cells has received only limited attention. This is particularly true in selectively cross-linked "tetra-PEG" hydrogels, whose design limits network inhomogeneities. Here, we used a combination of theoretical calculations, predictive modeling, and experimental measurements of hydrogel swelling, rheological behavior, and diffusion kinetics to characterize tetra-PEG hydrogels' permissiveness to the diffusion of molecules of biologically relevant size as we changed polymer concentration, and thus hydrogel mechanical strength. Our models predict that hydrogel mesh size has little effect on the diffusivity of model molecules and instead predicts that diffusion rates are more highly dependent on solute size. Indeed, our model predicts that changes in hydrogel mesh size only begin to have a non-negligible impact on the concentration of a solute that diffuses out of hydrogels for the smallest mesh sizes and largest diffusing solutes. Experimental measurements characterizing the diffusion of fluorescein isothiocyanate (FITC)-labeled dextran molecules of known size aligned well with modeling predictions and suggest that doubling the polymer concentration from 2.5% (w/v) to 5% produces stiffer gels with faster gelling kinetics without affecting the diffusivity of solutes of biologically relevant size but that 10% hydrogels can slow their diffusion. Our findings provide confidence that the stiffness of tetra-PEG hydrogels can be modulated over a physiological range without significantly impacting the transport rates of solutes to and from encapsulated cells.
Topics: Biocompatible Materials; Diffusion; Hydrogels; Polyethylene Glycols; Tissue Engineering
PubMed: 34151570
DOI: 10.1021/acsbiomaterials.0c01723