Search NASA⌕ Search

SEARCH · Search NASA

Results for “cell aggregation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Enabling high energy lithium metal batteries via single-crystal Ni-rich cathode material co-doping strategy

High-capacity Ni-rich layered oxides are promising cathode materials for secondary lithium-based battery systems. However, their structural instability detrimentally affects the battery performance during cell cycling. Here, we report an Al/Zr co-doped single-crystalline LiNi<:sub>0.88 Co 0.09 Mn 0.03 O 2 (SNCM) cathode material to circumvent the instability issue. We found that soluble Al ions are adequately incorporated in the SNCM lattice while the less soluble Zr ions are prone to aggregate in the outer SNCM surface layer. The synergistic effect of Al/Zr co-doping in SNCM lattice improve the Li-ion mobility, relief the internal strain, and suppress the Li/Ni cation mixing upon cycling at high cut-off voltage. These features improve the cathode rate capability and structural stabilization during prolonged cell cycling. In particular, the Zr-rich surface enables the formation of stable cathode-electrolyte interphase, which prevent SNCM from unwanted reactions with the non-aqueous fluorinated liquid electrolyte solution and avoid Ni dissolution. To prove the practical application of the Al/Zr co-doped SNCM, we assembled a 10.8 Ah pouch cell (using a 100 μm thick Li metal anode) capable of delivering initial specific energy of 504.5 Wh kg- 1 at 0.1 °C and 25 °C.

25 ENERGY STORAGE↗
DOE OSTI2021

Effects of Ink Formulation on Construction of Catalyst Layers for High-Performance Polymer Electrolyte Membrane Fuel Cells

Rational design of catalyst layers in a membrane electrode assembly (MEA) is crucial for achieving high-performance polymer electrolyte membrane fuel cells. Establishing a clear understanding of the property (catalyst ink)–structure (catalyst layer)–performance (MEA) relationship lays the foundation for this rational design. Here, a synergistic approach was taken to correlate the ink formulation, the microstructure of catalyst layers, and the resulting MEA performance to establish such a property–structure–performance relationship. The solvent composition (n-PA/H 2 O mixtures) demonstrated a strong influence on the performance of the MEA fabricated with an 830-EW (Aquivion) ionomer, especially polarization losses of cell activation and mass transport. The performance differences were studied in terms of how the solvent composition affects the catalyst/ionomer interface, ionomer network, and pore structure of the resulting catalyst layers. The ionomer aggregates mainly covered the surface of catalyst aggregates acting as oxygen reduction reaction active sites, and the aggregate sizes of the ionomer and catalyst (revealed by ultrasmall angle X-ray scattering and cryo-transmission electron microscopy) were dictated by tuning the solvent composition, which in turn determined the catalyst/ionomer interface (available active sites). In n-PA/H 2 O mixtures with 50~90 wt % H 2 O, the catalyst agglomerates could be effectively broken up into small aggregates, leading to enhanced kinetic activities. The boiling point of the mixed solvents determined the pore structure of ultimate catalyst layers, as evidenced by mercury porosimetry and scanning electron microscopy. For mixed solvents with a higher boiling point, the catalyst–ionomer aggregates in the ink tend to agglomerate during the solvent evaporation process and finally form larger catalyst–ionomer aggregates in the ultimate catalyst layer, resulting in more secondary pores and thus lower mass transport resistance. Both the enlarged catalyst/ionomer interface and appropriate pore structure were achieved with the catalyst layer fabricated from an n-PA/H 2 O mixture with 90 wt % H 2 O, leading to the best MEA performance.

25 ENERGY STORAGE↗
DOE OSTI2026

Molecular Tuning of Ether Cosolvent Chemistry for High-Voltage Sodium-Ion Batteries

Ethers as electrolyte cosolvents in sodium-ion batteries (SIBs) provide favorable Na + solvation and interfacial properties, but their low oxidative stability limits their use in high-voltage SIBs. Herein, we address this limitation via molecular tuning of ether cosolvents for high-voltage (4.2 V) hard carbon || NaNi 0.33 Fe 0.33 Mn 0.33 O 2 full cells. Tetrahydropyran (THP) is functionalized with a nitrile group to form tetrahydropyran-4-carbonitrile (THPCN). To delineate the effect of nitrile functionalization and benchmark ether against a conventional carbonate, THP, THPCN, and diethyl carbonate (DEC) are evaluated as cosolvents with ethylene carbonate. Nitrile functionalization lowers the HOMO energy of the ether, extends the electrolyte stability window, and alters Na⁺ solvation. Spectroscopic techniques and molecular dynamics simulations reveal that THPCN exhibits predominantly aggregate-dominated solvation (95.1 %) with weakened Na + -solvent interactions, producing the most anion-rich environment relative to DEC and THP cosolvents. THPCN-modified solvation promotes the formation of highly conductive, fluorine-enriched interphases that suppress parasitic reactions. Pouch full cells with THPCN sustained ~ 600 cycles at 4.2 V, outperforming THP and DEC. Operando gas analysis reveals that THPCN reduces CO 2 generation by 45% and H 2 generation by 30% relative to THP. Furthermore, the findings demonstrate nitrile functionalization as a molecular design strategy to stabilize ethers and enable high-voltage SIBs.

25 ENERGY STORAGE↗
NASA NTRS1995

The role of radiation hard solar cells in minimizing the costs of global satellite communications systems

An analysis embodied in a PC computer program is presented which quantitatively demonstrates how the availability of radiation hard solar cells can minimize the cost of a global satellite communication system. The chief distinction between the currently proposed systems, such as Iridium Odyssey and Ellipsat, is the number of satellites employed and their operating altitudes. Analysis of the major costs associated with implementing these systems shows that operation within the earth's radiation belts can reduce the total system cost by as much as a factor of two, so long as radiation hard components including solar cells, can be used. A detailed evaluation of several types of planar solar cells is given, including commercially available Si and GaAs/Ge cells, and InP/Si cells which are under development. The computer program calculates the end of life (EOL) power density of solar arrays taking into account the cell geometry, coverglass thickness, support frame, electrical interconnects, etc. The EOL power density can be determined for any altitude from low earth orbit (LEO) to geosynchronous (GEO) and for equatorial to polar planes of inclination. The mission duration can be varied over the entire range planned for the proposed satellite systems. An algorithm is included in the program for determining the degradation of cell efficiency for different cell technologies due to proton and electron irradiation. The program can be used to determine the optimum configuration for any cell technology for a particular orbit and for a specified mission life. Several examples of applying the program are presented, in which it is shown that the EOL power density of different technologies can vary by an order of magnitude for certain missions. Therefore, although a relatively radiation soft technology can be made to provide the required EOL power by simply increasing the size of the array, the impact on the total system budget could be unacceptable, due to increased launch and hardware costs. In aggregate these factors can account for more than a 10% increase in the total system cost. Since the estimated total costs of proposed global coverage systems range from $1 Billion to $9 Billion, the availability of radiation hard solar cells could make a decisive difference in the selection of a particular constellation architecture.

Summers, Geoffrey P.↗
DOE OSTI2022

Radiation-induced Alteration of Meta-chert

Concrete aggregate identified as “meta-chert” was irradiated with gamma-rays and neutrons. To identify the volume expansion of the aggregate under neutron irradiation, herein the following analyses were performed for pristine and irradiated α-quartz and meta-chert: X-ray diffraction (XRD)/Rietveld analysis, dimension change, water pycnometry, He-pycnometry, light optical microscopy (LOM), and scanning electron microscopy (SEM). From the difference of volume expansion observed from dimension change and water / helium pycnometry, the crack opening inside the aggregate subjected to irradiation was elucidated, and this was confirmed by LOM and SEM analysis. The crack contribution to the expansion of the aggregate was significant for neutron fluence > 6.99 × 1019 n/cm 2 , for E ≥ 0.01 MeV. Based on the XRD analysis, changes in lattice parameters were identified and the cell volume expansion was compared with the data by helium pycnometry. Based on the density change calculation and phase calculation data, the density of X-ray amorphous phase was consistent with that of expanded crystal α-quartz.

36 MATERIALS SCIENCE↗
NASA NTRS1994

Alpha-A crystallin: quantitation of C-terminal modification during lens aging

Previous studies have demonstrated that the C-terminal region of alpha-A crystallin is susceptible to age-dependent, posttranslational modification. To quantitate the amount of modification, alpha-A crystallin was purified from total proteins of the aging bovine lens, then digested with lys-C endoproteinase. Reverse phase, high pressure liquid chromatography was used to resolve and quantitate the resulting peptides, to determine the amount of C-terminal peptide relative to peptides from other regions of the protein that have not been reported to undergo modification. The results indicate that relative to alpha-A crystallin from newborn lens, posttranslational modification has occurred in approximately 45-55% of the C-terminal region from mature lens. These results demonstrate extensive modification of the C-terminal region of alpha-A crystallin from the mature lens, indicating that during the aging process, posttranslational modifications in this region may make significant contributions to the aggregated state and/or molecular chaperone properties of the molecule.

NASA Discipline Cell Biology↗
NASA NTRS1996

The role of radiation hard solar cells in minimizing the costs of global satellite communication systems

An analysis embodied in a PC computer program is presented, which quantitatively demonstrates how the availability of radiation hard solar cells can help minimize the cost of a global satellite communications system. An important distinction between the currently proposed systems, such as Iridium, Odyssey and Ellipsat, is the number of satellites employed and their operating altitudes. Analysis of the major costs associated with implementing these systems shows that operation at orbital altitudes within the earth's radiation belts (10(exp 3) to 10(exp 4)km) can reduce the total cost of a system by several hundred percent, so long as radiation hard components including solar cells can be used. A detailed evaluation of the predicted performance of photovoltaic arrays using several different planar solar cell technologies is given, including commercially available Si and GaAs/Ge, and InP/Si which is currently under development. Several examples of applying the program are given, which show that the end of life (EOL) power density of different technologies can vary by a factor of ten for certain missions. Therefore, although a relatively radiation-soft technology can usually provide the required EOL power by simply increasing the size of the array, the impact upon the total system budget could be unacceptable, due to increased launch and hardware costs. In aggregate, these factors can account for more than a 10% increase in the total system cost. Since the estimated total costs of proposed global-coverage systems range from $1B to $9B, the availability of radiation-hard solar cells could make a decisive difference in the selection of a particular constellation architecture.

Summers, Geoffrey P.↗
DOE OSTI2022

Electronic landscape of the f -electron intermetallics with the ThCr 2 Si 2 structure

Although strongly correlated f -electron systems are well known as reservoirs for quantum phenomena, a persistent challenge is to design specific states. What is often missing are simple ways to determine whether a given compound can be expected to exhibit certain behaviors and what tuning vector(s) would be useful to select the ground state. In this review, we address this question by aggregating information about Ce, Eu, Yb, and U compounds with the ThCr 2 Si 2 structure. We construct electronic/magnetic state maps that are parameterized in terms of unit cell volumes and d -shell filling, which reveals useful trends including that (i) the magnetic and nonmagnetic examples are well separated, and (ii) the crossover regions harbor the examples with exotic states. These insights are used to propose structural/chemical regions of interest in these and related materials, with the goal of accelerating discovery of the next generation of f -electron quantum materials.

42 ENGINEERING↗
NASA NTRS1995

Reverse Micelle Based Synthesis of Microporous Materials in Microgravity

Formation of zincophosphates from zinc and phosphate containing reverse micelles (water droplets in hexane) has been examined. The frameworks formed resemble that made by conventional hydrothermal synthesis. Dynamics of crystal growth are however quite different, and form the main focus of this study. In particular, the formation of zincophosphate with the sodalite framework was examined in detail. The intramicellar pH was found to have a strong influence on crystal growth. Crystals with a cubic morphology were formed directly from the micelles, without an apparent intermediate amorphous phase over a period of four days by a layer-bylayer growth at the intramicellar pH of 7.6. At a pH of 6.8, an amorphous precipitate rapidly sediments in hours. Sodalite was eventually formed from this settled phase via surface diffusion and reconstruction within four days. With a rotating cell, it was possible to minimize sedimentation and crystals were found to grow epitaxially from the spherical, amorphous particles. Intermediate pH's of 7.2 led to formation of aggregated sodalite crystals prior to settling, again without any indication of an intermediate amorphous phase. These diverse pathways were possible due to changes in intramicellar supersaturation conditions by minor changes in pH. In contrast, conventional syntheses in this pH range all proceeded by similar crystallization pathways through an amorphous gel. This study establishes that synthesis of microporous frameworks is not only possible in reverse micellar systems, but they also allow examination of possible crystallization pathways.

Dutta, Prabir K.↗
NASA NTRS2006

Human Bone-Forming Chondrocytes Cultured in the Hydrodynamic Focusing Bioreactor Retain Matrix Proteins: Similarities to Spaceflight Results

Fracture healing, crucial to a successful Mars mission, involves formation of a cartilaginous fracture callus which differentiates, mineralizes, ossifies and remodels via the endochondral process. Studies of spaceflown and tailsuspended rats found that, without loading, fracture callus formation and cartilage differentiation within the callus were minimal. We found delayed differentiation of chondrocytes within the rat growth plate on Cosmos 1887, 2044, and Spacelab 3. In the current study, differentiation of human bone-forming chondrocytes cultured in the hydrodynamic focusing bioreactor (HFB) was assessed. Human costochondral chondrocytes in suspension were aggregated overnight, then cultured in the HFB for 25 days. Collagen Type II, aggrecan and unsulfated chondroitin were found extracellularly and chondroitin sulfates 4 and 6 within the cell. Lack of secretion was also found in pancreatic cells of spaceflown rats, and in our SL3 studies. The HFB can be used to study cartilage differentiation in simulated microgravity.

Duke, P. J.↗
DOE OSTI2021

Engineering an efficient and bright split Corynactis californica green fluorescent protein

Split green fluorescent protein (GFP) has been used in a panoply of cellular biology applications to study protein translocation, monitor protein solubility and aggregation, detect protein–protein interactions, enhance protein crystallization, and even map neuron contacts. Recent work shows the utility of split fluorescent proteins for large scale labeling of proteins in cells using CRISPR, but sets of efficient split fluorescent proteins that do not cross-react are needed for multiplexing experiments. We present a new monomeric split green fluorescent protein (ccGFP) engineered from a tetrameric GFP found in Corynactis californica, a bright red colonial anthozoan similar to sea anemones and scleractinian stony corals. Split ccGFP from C. californica complements up to threefold faster compared to the original Aequorea victoria split GFP and enable multiplexed labeling with existing A. victoria split YFP and CFP.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A re-examination of the mechanism of whiting events: A new role for diatoms in Fayetteville Green Lake (New York, USA)

Whiting events—the episodic precipitation of fine-grained suspended calcium carbonates in the water column—have been documented across a variety of marine and lacustrine environments. Whitings likely are a major source of carbonate muds, a constituent of limestones, and important archives for geochemical proxies of Earth history. While several biological and physical mechanisms have been proposed to explain the onset of these precipitation events, no consensus has been reached thus far. Fayetteville Green Lake (New York, USA) is a meromictic lake that experiences annual whitings. Materials suspended in the water column collected through the whiting season were characterized using scanning electron microscopy and scanning transmission X-ray microscopy. Whitings in Fayetteville Green Lake are initiated in the spring within the top few meters of the water column, by precipitation of fine amorphous calcium carbonate (ACC) phases nucleating on microbial cells, as well as on abundant extracellular polymeric substances (EPS) frequently associated with centric diatoms. Whiting particles found in the summer consist of 5–7 μm calcite grains forming aggregates with diatoms and EPS. Simple calculations demonstrate that calcite particles continuously grow over several days, then sink quickly through the water column. In the late summer, partial calcium carbonate dissolution is observed deeper in the water column. Settling whiting particles, however, reach the bottom of the lake, where they form a major constituent of the sediment, along with diatom frustules. The role of diatoms and associated EPS acting as nucleation surfaces for calcium carbonates is described for the first time here as a potential mechanism participating in whitings at Fayetteville Green Lake. This mechanism may have been largely overlooked in other whiting events in modern and ancient environments.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1974

Study to define behavior of liquid lubricants in an elastohydrodynamic contact

The spectra of an ester and a saturated hydrocarbon polymer were obtained at pressures ranging from ambient to 2 GN/sq m (20 kilobar) and at temperatures between ambient and 180 C in absorption and between 150 C and 210 C in emission. To simulate contact conditions the fluids were contained in the tiny sample volume of a diamond cell, i.e., the hole in a metal spacer separating two diamonds pressed against each other in a nut crackerlike arrangement. Pressures could be deduced from bandshifts and states of aggregation from bandwidths in the fluorescence spectrum of a ruby crystal immersed in the fluids. An infrared Fourier transform spectrometer was used with attachments specially designed to analyze the radiation passed through the sample and both diamonds (absorption technique) or the radiation emanating from the heated sample and passing through only one diamond (emission technique). The latter technique is applicable to operating EHD contacts. Spectral changes pointing to possible glass transitions and composition changes were observed. Emission and absorption spectra were generally equivalent. Some emission bandshapes appear to be temperature sensitive enough to be useful as internal temperature probes.

Lauer, J. L.↗
NASA NTRS2019

The Omics of Stem Cell Mediated Regeneration: A Pilot Single Cell RNA-Seq Study of Mechanotransduction

Mechanical forces are potent modulators of stem cell based tissue regenerative mechanisms, inducing cell fate decisions and tissue specific commitment. A unique platform for investigating mechanotransduction is spaceflight, where microgravity and altered fluid mechanics provide a loading-null experimental condition. Seminal investigations of regenerative capacity in a wholly regenerative species, the newt model, and in a variety of totipotent and adult stem cell populations have demonstrated the detrimental effects of unloading on maintenance of stem cell based regeneration. Of particular interest is the observation that unloading interferes with the transition of stem cell pools from proliferative state to differentiation commitment. In this work we sought to test the hypothesis that gravity mechanotransduction regulates stem cell tissue regenerative processes by modulating stem cell proliferation and differentiation fates at specific cell cycle stages. To do this, clonally-derived ESCs were plated on a collagen matrix and expanded for 36 hours before re-plating on a non-adherent culture dish in the absence of leukemia inhibitory factor (LIF) to form spheroid aggregate EBs. After formation, the EBs were transferred to a collagen matrix coated culture dishes and given 4 days to allow implantation and outgrowth. In parallel, totipotent ESCs were plated 24 hours before mechanical stimulation on collagen matrix culture dishes in the presence of LIF to maintain totipotency and serve as un-differentiation committed controls. The EBs and ESCs were then subjected to either a 60 minute pulse of gravity (static loading) or 60 minutes of cyclic stretch (dynamic loading) mechanotransduction. Six hours post-stimulation, we used a 10X Genomics Single Cell controller to generate bar-coded single cell Illumina libraries and sequenced expressomes for 5,000 static loaded cells, representative of a change in gravity mechanotransduction, 5,000 dynamic loaded cells, representative of tissue loading associate with physiologic function, and 5,000 unstimulated 1g control cells. The comparison of these 3 libraries by cluster assignment based on like gene expression patterns show substantial alteration in cluster geometry due to mechanical loading. Specifically the mechanically loaded EB outgrowth cells to retain potency markers (PAX6, SOX2, CD34) and suppress early commitment markers (Dhh, VCAN, Igf1). Whereas the EBs cultured under the non-stimulated conditions display clear departure from the ESC expressome with lineage commitment markers upregulated and several tissue specific markers being expressed (BMP "early musculoskeletal development, Mesp1" early cardiovascular cell lineage). These markers are not seen in the mechano-stimulated cultures or the totipotent ESC cultures. Comparison of like clusters between our experimental conditions revealed an array of regenerative and stem cell genes are significantly mechano-regulated. Of particular importance CDKN1a/p21, a gene shown by previous investigation of our research team to be significantly upregulated in unloading, was suppressed in the static and dynamic loaded EBS. In addition to CDKN1a/p21 many genes related to cell cycle and transitory differentiation markers had elevated expression in the mechano-stimulated EBs, but surprisingly these trends were not observed in the ESC cultures. This study is the first of its kind investigating for mechano-signaling and mechano-regulated pathways, and has alre

Single cell RNA-sequecing↗
DOE OSTI2021

Heat shock induces the nuclear accumulation of YAP1 via SRC

Highlights: • YAP1 enters the nucleus in response to heat shock. • YAP1 spontaneously returns to the cytoplasm after heat shock. • SRC is involved in the nuclear accumulation of YAP1. • HSP90 is involved in the return to the cytoplasm of YAP1. • YAP1 cross-talks with NF-κB signaling in response to heat shock. Yes-associated protein 1 (YAP1), a co-transcription activator, shuttles between the cytoplasm and the nucleus. Phosphorylation by large tumor suppressor kinases (LATS1/2) is the major determinant of YAP1 subcellular localization. Unphosphorylated YAP1 interacts with transcription factors in the nucleus and regulates gene transcription, while phosphorylated YAP1 is trapped in the cytoplasm and is degraded. We found that when U2OS and HeLa cells are exposed to 42 °C, YAP1 enters the nucleus within 30 min and returns to the cytoplasm at 4 h. SRC and HSP90 are involved in nuclear accumulation and return to the cytoplasm, respectively. Upon heat shock, LATS2 forms aggregates including protein phosphatase 1 and is dephosphorylated and inactivated. SRC activation is necessary for the formation of aggregates, while HSP90 is required for their dissociation. YAP1 is involved in heat shock-induced NF-κB signaling. Mechanistically, YAP1 is implicated in strengthening the interaction between RELA and DPF3, a component of SWI/SNF chromatin remodeling complex, in response to heat shock. Thus, YAP1 plays a role as a thermosensor.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Poly(vinyl alcohol) Hydrogels with Broad-Range Tunable Mechanical Properties via the Hofmeister Effect

Hydrogels, exhibiting wide applications in soft robotics, tissue engineering, implantable electronics, etc., often require sophisticately tailoring of the hydrogel mechanical properties to meet specific demands. For examples, soft robotics necessitates tough hydrogels; stem cell culturing demands various tissue-matching modulus; and neuron probes desire dynamically tunable modulus. Herein, a strategy to broadly alter the mechanical properties of hydrogels reversibly via tuning the aggregation states of the polymer chains by ions based on the Hofmeister effect is reported. An ultratough poly(vinyl alcohol) (PVA) hydrogel as an exemplary material (toughness 150 ± 20 MJ m -3 ), which surpasses synthetic polymers like poly(dimethylsiloxane), synthetic rubber, and natural spider silk is fabricated. With various ions, the hydrogel's various mechanical properties are continuously and reversibly in situ modulated over a large window: tensile strength from 50 ± 9 kPa to 15 ± 1 MPa, toughness from 0.0167 ± 0.003 to 150 ± 20 MJ m -3 , elongation from 300 ± 100% to 2100 ± 300%, and modulus from 24 ± 2 to 2500 ± 140 kPa. Importantly, the ions serve as gelation triggers and property modulators only, not necessarily required to remain in the gel, maintaining the high biocompatibility of PVA without excess ions. Overall, this strategy, enabling high mechanical performance and broad dynamic tunability, presents a universal platform for broad applications from biomedicine to wearable electronics.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Harnessing Particle Size‐Control and DNA‐Oligo Functionalization in ZIF‐76 for Biological Applications

Abstract Advanced therapeutics require novel nanocarriers to ensure their functionality is preserved during transit. Zeolitic imidazolate frameworks (ZIFs) have emerged as promising materials in this field owing to their combined biocompatibility, high porosity, and tunable chemistry. While a diverse family of ZIFs has been reported, few have been explored beyond the prototypical ZIF‐8. Herein, the size‐controlled synthesis of three distinct ZIF‐76 analogs is demonstrated, overcoming the unique synthetic challenges intrinsic to the lta topology and complex crystallization kinetics associated with the mixed linker approach. This assesses the materials’ platform effectiveness for intracellular delivery first by exploring the structural and colloidal stability in biologically relevant media. To circumvent particle aggregation, fluorescently labeled DNA oligonucleotides are post‐synthetically attached to the ZIF surface. This modification significantly improves the colloidal stability in media and facilitates particle internalization tracking. Finally, the particle‐cell interactions are assessed, revealing rapid cell membrane association with macrophages, but not lung epithelial cells, and ZIF accumulation within macrophages which increased over time. Importantly, this study outlines a generalized approach toward expanding the available library of ZIFs for biological applications, enabling the potential for targeted therapeutic delivery for intracellular infections treatment.

Deneff, Jacob I.↗
DOE OSTI2025

Subventricular Accumulation of Cu in the Aging Mouse Brain Does Not Associate with Anticipated Increases in Markers of Oxidative Stress

Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer’s disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles. In our study herein, we have characterized lateral ventricle Cu content in a unique murine model of accelerated aging, senescence accelerated mouse-prone 8 (SAMP8) mice. Our results confirm an age-related increase in ventricle Cu content, consistent with the studies by others in wild-type mice and rats. Specifically, we observed Cu content to increase over the time frame 1 to 5 months and 5 to 9 months, but interestingly, no significant increase occurred between 9 and 12 months (although brain Cu content at 12 months was significantly elevated relative to 1 and 5 month-old animals). Despite the magnitude of Cu increase observed within the cells that comprise the subventricular zone of lateral ventricles (average 3 mM Cu, with isolated subcellular concentrations of 17 mM), we did not detect spectroscopic markers of thiol oxidation, protein aggregation, or lipid oxidation. The lack of evidence for oxidative stress in ex vivo animal tissue is in contrast to in vitro studies demonstrating that thiol, protein, and lipid oxidation is pronounced at these Cu concentrations. We suggest that our findings most likely indicate that the Cu ions in this brain region are sequestered in an unreactive form, possibly extended chains of Cu-thiolate complexes, which do not readily redox cycle in the aqueous cytosol. In conclusion, these results also appear to partially challenge the long-held view that age-related increases in brain metal content drive oxidative stress as we did not observe a concomitant association between age-related Cu increase and markers of oxidative stress, nor did we observe a net increase in Cu content between mice aged 9 and 12 months.

X-ray fluorescence↗