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- Gyan, D. S., et al.
(författare)
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Low-temperature nanoscale heat transport in a gadolinium iron garnet heterostructure probed by ultrafast x-ray diffraction
- 2022
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Ingår i: Structural Dynamics-Us. - : AIP Publishing. - 2329-7778. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved x-ray diffraction has been used to measure the low-temperature thermal transport properties of a Pt/Gd3Fe5O12//Gd3Ga5O12 metal/oxide heterostructure relevant to applications in spin caloritronics. A pulsed femtosecond optical signal produces a rapid temperature rise in the Pt layer, followed by heat transport into the Gd3Fe5O12 (GdIG) thin film and the Gd3Ga5O12 (GGG) substrate. The time dependence of x-ray diffraction from the GdIG layer was tracked using an accelerator-based femtosecond x-ray source. The ultrafast diffraction measurements probed the intensity of the GdIG (1 -1 2) x-ray reflection in a grazing-incidence x-ray diffraction geometry. The comparison of the variation of the diffracted x-ray intensity with a model including heat transport and the temperature dependence of the GdIG lattice parameter allows the thermal conductance of the Pt/GdIG and GdIG//GGG interfaces to be determined. Complementary synchrotron x-ray diffraction studies of the low-temperature thermal expansion properties of the GdIG layer provide a precise calibration of the temperature dependence of the GdIG lattice parameter. The interfacial thermal conductance of the Pt/GdIG and GdIG//GGG interfaces determined from the time-resolved diffraction study is of the same order of magnitude as previous reports for metal/oxide and epitaxial dielectric interfaces. The thermal parameters of the Pt/GdIG//GGG heterostructure will aid in the design and implementation of thermal transport devices and nanostructures. (C) 2022 Author(s).
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- Herland, Anna, et al.
(författare)
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Proteomic and Metabolomic Characterization of Human Neurovascular Unit Cells in Response to Methamphetamine
- 2020
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Ingår i: ADVANCED BIOSYSTEMS. - : Wiley. - 2366-7478. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- The functional state of the neurovascular unit (NVU), composed of the blood-brain barrier and the perivasculature that forms a dynamic interface between the blood and the central nervous system (CNS), plays a central role in the control of brain homeostasis and is strongly affected by CNS drugs. Human primary brain microvascular endothelium, astrocyte, pericyte, and neural cell cultures are often used to study NVU barrier functions as well as drug transport and efficacy; however, the proteomic and metabolomic responses of these different cell types are not well characterized. Culturing each cell type separately, using deep coverage proteomic analysis and characterization of the secreted metabolome, as well as measurements of mitochondrial activity, the responses of these cells under baseline conditions and when exposed to the NVU-impairing stimulant methamphetamine (Meth) are analyzed. These studies define the previously unknown metabolic and proteomic profiles of human brain pericytes and lead to improved characterization of the phenotype of each of the NVU cell types as well as cell-specific metabolic and proteomic responses to Meth.
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- Maoz, Ben M., et al.
(författare)
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A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells
- 2018
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 36:9, s. 865-
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Tidskriftsartikel (refereegranskat)abstract
- The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood-brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.
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- Park, Tae-Eun, et al.
(författare)
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Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies
- 2019
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.
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