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Fluids and Barriers of the CNS Mar 2023Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of...
BACKGROUND
Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport.
METHODS
We derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data.
RESULTS
We provide structural-functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the range [Formula: see text] to [Formula: see text], diffusion membrane coefficients for small solutes in the range [Formula: see text] to [Formula: see text], and gap area fractions in the range 0.2-0.6%, based on a inter-endfoot gap width of 20 nm.
CONCLUSIONS
The astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than those of the extra-cellular matrix while being two orders of magnitude higher than those of the vessel wall.
Topics: Mice; Animals; Astrocytes; Brain; Biological Transport; Diffusion; Extracellular Space
PubMed: 36941607
DOI: 10.1186/s12987-023-00421-8 -
Environmental Science & Technology May 2024Molecular diffusion of chemical species in subsurface environments─rock formations, soil sediments, marine, river, and lake sediments─plays a critical role in a...
Molecular diffusion of chemical species in subsurface environments─rock formations, soil sediments, marine, river, and lake sediments─plays a critical role in a variety of dynamic processes, many of which affect water chemistry. We investigate and demonstrate the occurrence of anomalous (non-Fickian) diffusion behavior, distinct from classically assumed Fickian diffusion. We measured molecular diffusion through a series of five chalk and dolomite rock samples over a period of about two months. We demonstrate that in all cases, diffusion behavior is significantly different than Fickian. We then analyze the results using a continuous time random walk framework that can describe anomalous diffusion in heterogeneous porous materials such as rock. This methodology shows extreme long-time tailing of tracer advance as compared to conventional Fickian diffusion processes. The finding that distinct anomalous diffusion occurs ubiquitously implies that diffusion-driven processes in subsurface zones should be analyzed using tools that account for non-Fickian diffusion.
Topics: Diffusion; Porosity; Geologic Sediments
PubMed: 38736287
DOI: 10.1021/acs.est.4c01386 -
Advances in Experimental Medicine and... 2020Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O in tissue depends on its... (Review)
Review
Oxygen delivery to tissue mitochondria relies on simple diffusion in the target cells and tissues. As such, intracellular availability of O in tissue depends on its solubility and diffusivity in complex and heterogeneous macromolecular environments. The path of oxygen diffusion is key to its rate of transfer, especially where pathways of differing favorability are present. Most commonly, aqueous media, such as interstitial fluid and cytoplasm, are assumed to provide the dominant diffusion path. Here, the 'hydrophobic channeling' hypothesis is revisited, and several lines of evidence pointing toward lipid-accelerated oxygen diffusion pathways are discussed. The implications of hydrophobic channeling are considered in light of extended membrane networks in cells and tissues.
Topics: Cells; Diffusion; Hydrophobic and Hydrophilic Interactions; Lipid Metabolism; Lipids; Mitochondria; Oxygen
PubMed: 31893409
DOI: 10.1007/978-3-030-34461-0_23 -
International Journal of Molecular... Oct 2022The mechanisms of transport of substances in the brain parenchyma have been a hot topic in scientific discussion in the past decade. This discussion was triggered by the... (Review)
Review
The mechanisms of transport of substances in the brain parenchyma have been a hot topic in scientific discussion in the past decade. This discussion was triggered by the proposed glymphatic hypothesis, which assumes a directed flow of cerebral fluid within the parenchyma, in contrast to the previous notion that diffusion is the main mechanism. However, when discussing the issue of "diffusion or non-diffusion", much less attention was given to the question that diffusion itself can have a different character. In our opinion, some of the recently published results do not fit into the traditional understanding of diffusion. In this regard, we outline the relevant new theoretical approaches on transport processes in complex random media such as concepts of diffusive diffusivity and time-dependent homogenization, which expands the understanding of the forms of transport of substances based on diffusion.
Topics: Extracellular Space; Brain; Diffusion; Biological Transport; Diffusion Magnetic Resonance Imaging
PubMed: 36293258
DOI: 10.3390/ijms232012401 -
Magnetic Resonance in Medicine Dec 2021Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article... (Review)
Review
Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article reviews an emerging paradigm that has the potential to provide a more detailed assessment of tissue microstructure-combined diffusion-relaxometry imaging. Combined diffusion-relaxometry acquisitions vary multiple MR contrast encodings-such as b-value, gradient direction, inversion time, and echo time-in a multidimensional acquisition space. When paired with suitable analysis techniques, this enables quantification of correlations and coupling between multiple MR parameters-such as diffusivity, , , and . This opens the possibility of disentangling multiple tissue compartments (within voxels) that are indistinguishable with single-contrast scans, enabling a new generation of microstructural maps with improved biological sensitivity and specificity.
Topics: Brain; Diffusion; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Models, Theoretical
PubMed: 34411331
DOI: 10.1002/mrm.28963 -
Biochimica Et Biophysica Acta Oct 2016Cellular membranes are typically decorated with a plethora of embedded and adsorbed macromolecules, e.g. proteins, that participate in numerous vital processes. With... (Review)
Review
Cellular membranes are typically decorated with a plethora of embedded and adsorbed macromolecules, e.g. proteins, that participate in numerous vital processes. With typical surface densities of 30,000 proteins per μm(2) cellular membranes are indeed crowded places that leave only few nanometers of private space for individual proteins. Here, we review recent advances in our understanding of protein crowding in membrane systems. We first give a brief overview on state-of-the-art approaches in experiment and simulation that are frequently used to study crowded membranes. After that, we review how crowding can affect diffusive transport of proteins and lipids in membrane systems. Next, we discuss lipid and protein sorting in crowded membrane systems, including effects like protein cluster formation, phase segregation, and lipid droplet formation. Subsequently, we highlight recent progress in uncovering crowding-induced conformational changes of membranes, e.g. membrane budding and vesicle formation. Finally, we give a short outlook on potential future developments in the field of crowded membrane systems. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Topics: Cell Membrane; Diffusion; Membrane Lipids; Membrane Proteins; Molecular Conformation
PubMed: 26724385
DOI: 10.1016/j.bbamem.2015.12.021 -
Magnetic Resonance in Medicine Jul 2022Relationships between diffusion-weighted MRI signals and hepatocyte microstructure were investigated to inform liver diffusion MRI modeling, focusing on the following...
PURPOSE
Relationships between diffusion-weighted MRI signals and hepatocyte microstructure were investigated to inform liver diffusion MRI modeling, focusing on the following question: Can cell size and diffusivity be estimated at fixed diffusion time, realistic SNR, and negligible contribution from extracellular/extravascular water and exchange?
METHODS
Monte Carlo simulations were performed within synthetic hepatocytes for varying cell size/diffusivity / , and clinical protocols (single diffusion encoding; maximum b-value: {1000, 1500, 2000} s/mm ; 5 unique gradient duration/separation pairs; SNR = { , 100, 80, 40, 20}), accounting for heterogeneity in and perfusion contamination. Diffusion ( ) and kurtosis ( ) coefficients were calculated, and relationships between and were visualized. Functions mapping to were computed to predict unseen values, tested for their ability to classify discrete cell-size contrasts, and deployed on 9.4T ex vivo MRI-histology data of fixed mouse livers RESULTS: Relationships between and are complex and depend on the diffusion encoding. Functions mapping to captures salient characteristics of and dependencies. Mappings are not always accurate, but they enable just under 70% accuracy in a three-class cell-size classification task (for SNR = 20, = 1500 s/mm , = 20 ms, and = 75 ms). MRI detects cell-size contrasts in the mouse livers that are confirmed by histology, but overestimates the largest cell sizes.
CONCLUSION
Salient information about liver cell size and diffusivity may be retrieved from minimal diffusion encodings at fixed diffusion time, in experimental conditions and pathological scenarios for which extracellular, extravascular water and exchange are negligible.
Topics: Animals; Contrast Media; Diffusion; Diffusion Magnetic Resonance Imaging; Hepatocytes; Magnetic Resonance Imaging; Mice; Water
PubMed: 35181943
DOI: 10.1002/mrm.29174 -
Progress in Biophysics and Molecular... Aug 2017Since Robert Brown's first observations of random walks by pollen particles suspended in solution, the concept of diffusion has been subject to countless theoretical and... (Review)
Review
Since Robert Brown's first observations of random walks by pollen particles suspended in solution, the concept of diffusion has been subject to countless theoretical and experimental studies in diverse fields from finance and social sciences, to physics and biology. Diffusive transport of macromolecules in cells is intimately linked to essential cellular functions including nutrient uptake, signal transduction, gene expression, as well as DNA replication and repair. Advancement in experimental techniques has allowed precise measurements of these diffusion processes. Mathematical and physical descriptions and computer simulations have been applied to model complicated biological systems in which anomalous diffusion, in addition to simple Brownian motion, was observed. The purpose of this review is to provide an overview of the major physical models of anomalous diffusion and corresponding experimental evidence on the target search problem faced by DNA-binding proteins, with an emphasis on DNA repair proteins and the role of anomalous diffusion in DNA target recognition.
Topics: Animals; DNA Repair; DNA-Binding Proteins; Diffusion; Humans; Protein Conformation
PubMed: 27939760
DOI: 10.1016/j.pbiomolbio.2016.12.004 -
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 -
Philosophical Transactions. Series A,... Dec 2021In the nearly seven decades since the publication of Alan Turing's work on morphogenesis, enormous progress has been made in understanding both the mathematical and... (Review)
Review
In the nearly seven decades since the publication of Alan Turing's work on morphogenesis, enormous progress has been made in understanding both the mathematical and biological aspects of his proposed reaction-diffusion theory. Some of these developments were nascent in Turing's paper, and others have been due to new insights from modern mathematical techniques, advances in numerical simulations and extensive biological experiments. Despite such progress, there are still important gaps between theory and experiment, with many examples of biological patterning where the underlying mechanisms are still unclear. Here, we review modern developments in the mathematical theory pioneered by Turing, showing how his approach has been generalized to a range of settings beyond the classical two-species reaction-diffusion framework, including evolving and complex manifolds, systems heterogeneous in space and time, and more general reaction-transport equations. While substantial progress has been made in understanding these more complicated models, there are many remaining challenges that we highlight throughout. We focus on the mathematical theory, and in particular linear stability analysis of 'trivial' base states. We emphasize important open questions in developing this theory further, and discuss obstacles in using these techniques to understand biological reality. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.
Topics: Diffusion; Mathematics; Models, Biological; Morphogenesis
PubMed: 34743603
DOI: 10.1098/rsta.2020.0268