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NASA NTRS2018

Aerogel-Based Insulation Materials for Cryogenic Applications

Many different aerogel-based materials are now being used in thermal insulation systems for cryogenic applications. These materials include flexible composite blankets, bulk-fill particles, and polymer composites in both evacuated and non-evacuated environments. In ambient environments, aerogels provide superior thermal performance compared to conventional polymeric foam and cellular glass insulations while offering unique advantages in solving problems with weathering, moisture, and mechanical damage. Aerogels are also used as spacer materials in multilayer insulation systems. These layered systems provide combined structural-thermal capability for cryogenic systems in either vacuum-jacketed or externally-applied insulation designs. Test data (effective thermal conductivity) include a wide range of both commercial and experimental aerogel materials. Testing was performed using laboratory cryostats and standard methods including full range vacuum (from ambient pressure to high vacuum) and boundary temperatures 293 K and 78 K. Examples of aerogel-based insulation systems are given for both evacuated and non-evacuated applications.

aerogel layered composites↗

DOE OSTI2023

Dissecting the Division of Labor in Microbial Consortia for the Production of Biofuels and Chemicals (Final Technical Report)

The overarching objective of this project is to elucidate the fundamental design rules for microbial division of labor (DOL), the core of ecosystem organization, in the context of artificial yeast—lactic acid bacteria consortia that produce advanced biofuel and chemical from cellulosic biomass. Over the course of four years, we have successfully achieved the objective through three lines of research that combines experiment with mathematical modeling. Specifically, we have shown that compositional and temporal DOL is effective in modulating mixed sugar fermentation by an engineered consortium and uncovered general quantitative criteria for conditions under which microbial DOL outperforms single superbugs for simultaneous utilization of mixed substrates. We also demonstrated, in synthetic consortia of yeast and lactic acid bacteria, that partitioning the labor for substrate breakdown and end-product synthesis can allow an efficient production of 2-butanol that is difficult otherwise for a single yeast strain. Additionally, by systematically probing the stability of an engineered cooperative consortium, we found that the stability of microbial symbiosis is governed by the topological structure of the underlying cellular interactions rather than specific microbial species and that rational modulation of the interactions may facilitate the restoration of collapsed consortia as well as the intervention of target communities. Together, this project has advanced the fundamental knowledge of microbial DOL in terms of its strength in mixed substrate fermentation, production of complex chemicals, and ecological system stability in the context of microbial consortia. It also provides valuable insights into the design, construction and optimization of artificial consortia for the utilization of cellulosic biomass and economic production of biofuel and chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2004

Flow of Fluid and Particle Assemblages in Rotating Systems

NASA-designed bioreactors have been highly successful in growing three-dimensional tissue structures in a low shear environment both on earth and in space. The goal of the present study is to characterize the fluid flow environment within the HFB-S bioreactor and determine the spatial distribution of particles that mimic cellular tissue structures. The results will be used to obtain optimal operating conditions of rotation rates and media perfusehnfuse rates which are required for cell culture growth protocols. Two types of experiments have been performed so far. First, we have performed laser florescent dye visualization of the perfusion loop to determine the mixing times within the chamber. The second type of experiments involved particles which represent cellular tissue to determine the spatial distribution with the chamber. From these experiments we established that mixing times were largely dependant on the speed ratio and sign of the difference between the spinner and the dome. The shortest mixing times occurred when the spinner rotates faster than the dome and longest mixing times occurs with no relative motion between the dome and spinner. Also, we have determined the spatial and temporal distribution of particle assemblages within the chamber.

Kizito, John↗

DOE OSTI2022

Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models

WD repeat domain 5 (WDR5) is a core scaffolding component of many multiprotein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is a component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin at tumor-critical target genes. As a part of these complexes, WDR5 plays a role in sustaining oncogenesis in a variety of human cancers that are often associated with poor prognoses. Thus, WDR5 has been recognized as an attractive therapeutic target for treating both solid and hematological tumors. Previously, small-molecule inhibitors of the WDR5-interaction (WIN) site and WDR5 degraders have demonstrated robust in vitro cellular efficacy in cancer cell lines and established the therapeutic potential of WDR5. However, these agents have not demonstrated significant in vivo efficacy at pharmacologically relevant doses by oral administration in animal disease models. We have discovered WDR5 WIN-site inhibitors that feature bicyclic heteroaryl P 7 units through structure-based design and address the limitations of our previous series of small-molecule inhibitors. Importantly, our lead compounds exhibit enhanced on-target potency, excellent oral pharmacokinetic (PK) profiles, and potent dose-dependent in vivo efficacy in a mouse MV4:11 subcutaneous xenograft model by oral dosing. Furthermore, these in vivo probes show excellent tolerability under a repeated high-dose regimen in rodents to demonstrate the safety of the WDR5 WIN-site inhibition mechanism. Collectively, our results provide strong support for WDR5 WIN-site inhibitors to be utilized as potential anticancer therapeutics.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2001

Molecular Simulations in Astrobiology

One of the main goals of astrobiology is to understand the origin of cellular life. In the absence of any record of the earliest ancestors of contemporary cells, protocells, the most direct way to test our understanding of their characteristics is to construct laboratory models of protocells. Such efforts, currently underway in the NASA Astrobiology Program, are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs of molecules that are capable of performing protocellular functions. Many of these functions, such as importing nutrients, capturing and storing energy, and responding to changes in the environment, are carried out by proteins bound to membranes. We use computer simulations to address the following, questions about these proteins: (1) How do small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes? (2) How do peptides aggregate to form membrane-spannin(y structures (e.g., channels)? (3) By what mechanisms do such aggregates perform their functions? The simulations are performed using the molecular dynamics (MD) method. In this method, Newton's equations of motion for each atom in the system are solved iteratively. At each time step, the forces exerted on each atom by the remaining atoms are evaluated by dividing them into two parts. Short-range forces are calculated directly in real space while long-range forces are evaluated in reciprocal space, usually using a particle-mesh algorithm which is of order O(NlnN). Currently, a time step of 2 femtoseconds is typically used, thereby making studies of problems occurring on multi-nanosecond time scales (10(exp 6) - 10(exp 8) time steps) accessible. To address a broader range of problems, simulations need to be extended by three orders of magnitude. Such an extension requires both algorithmic improvements and codes scalable to a large number of parallel processors. Work in this direction is in progress. Two specific series of simulations that demonstrate how peptides self-organize and function in membranes are discussed. In one series of simulations, it was shown that nonpolar peptides, disordered in water, translocate to the nonpolar interior of the membrane and, simultaneously, fold into two different helical structures, which remain in equilibrium. Once in the membrane, the peptides can readily change their orientation, especially in response to local electric fields. This structural and orientational flexibility of peptides with changing conditions may have provided a mechanism of transmitting signals between the environment and the interior of the protocell. In another series of simulations, the mechanism by which a simple protein channel efficiently mediates proton transport across membranes was investigated. This process is a key step in cellular bioenergetics. In the channel under study, proton transport is gated by four histidines that occlude the channel pore. The simulations demonstrate that protons move through the gate by a "shuttle" mechanism, wherein one histidine is protonated on the extracellular side and, subsequently, the proton bound on the opposite side is released.

Pohorille, Andrew↗

DOE OSTI2023

Smart Droplets Stabilized by Designer Surfactants: From Biomimicry to Active Motion to Materials Healing

The science and technologies of emulsion droplets have been a long‐term focus of extensive research endeavors for their practical utility across a breadth of industries, including pharmaceutical products, oil recovery processes, and the food sciences. However, with advances in materials chemistry and characterization tools, new emerging areas are arising with a focus on “smart droplets”. The versatility of emulsion droplets across is based on their ability to partition and create isolated systems with properties defined by the liquid–liquid interface, while preparative routes allow manipulation of droplet size, stability, and encapsulated contents. As described in this article, significant efforts are being devoted to creating new types of droplets by “activating” this interface through the incorporation of reactive structures that trigger droplet response to applied or environmental stimuli (e.g., pH, temperature, salt, or external fields). Moreover, parallels between droplets and live cells inspire efforts to conceive systems that resemble biological motifs or that can produce cellular behaviors that imitate biology (e.g., swarming, communication, or motion). Here, the authors highlight recent advances in smart droplets, with emphasis on organic, polymer, and/or particle surfactants that give rise to inter‐droplet communication (via aggregation, fusion, division, or mass transfer), droplet vehicles for controlled delivery, autonomous droplet motion, and tunable emulsion inversion. Especially emphasized is the macromolecular design to produce reactive and functional surfactants, which are crucial to responsive droplet behavior and their underlying mechanisms. More generally, the exquisite interplay between materials science and biology inspires the review of this research area that provides unique opportunities for insight and inspiration into the capabilities of new droplet designs.

36 MATERIALS SCIENCE↗

DOE OSTI2025

Discovery of Macrocyclic Myeloid Cell Leukemia 1 (Mcl-1)Inhibitors that Demonstrate Potent Cellular Efficacy and In Vivo Activity in a Mouse Solid Tumor Xenograft Model

Abstract The B cell lymphoma 2 (Bcl-2) family of proteins are key regulators of intrinsic apoptosis. The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1), which is associated with high tumor grade, poor survival, and resistance to treatment, has emerged as a promising candidate for treating hematological and solid cancers. Herein, we report the structure-guided design of small molecule macrocyclic Mcl-1 inhibitors based on the (R)-methyl-dihydropyrazinoindolone scaffold our group has previously disclosed. The macrocyclic inhibitors bind Mcl-1 with subnanomolar affinity and offer improved potency in cell culture growth inhibition assays. Inhibitor 13 achieved tumor regression in a lung cancer-derived tumor xenograft model in mice as a monotherapy. The improved potency of the macrocyclic series allowed replacement of heretofore conserved indole carboxylic acid moiety, resulting in neutral inhibitors. Amide inhibitor 25 displayed a >10-fold increase in oral bioavailability as compared to acid-containing macrocyclic or acyclic inhibitors.

Pharmacology & Pharmacy↗

NASA NTRS2015

Periodic Cellular Structure Technology for Shape Memory Alloys

Shape memory alloys are being considered for a wide variety of adaptive components for engine and airframe applications because they can undergo large amounts of strain and then revert to their original shape upon heating or unloading. Transition45 Technologies, Inc., has developed an innovative periodic cellular structure (PCS) technology for shape memory alloys that enables fabrication of complex bulk configurations, such as lattice block structures. These innovative structures are manufactured using an advanced reactive metal casting technology that offers a relatively low cost and established approach for constructing near-net shape aerospace components. Transition45 is continuing to characterize these structures to determine how best to design a PCS to better exploit the use of shape memory alloys in aerospace applications.

Chen, Edward Y.↗

DOE OSTI2024

Parameter development and characterization of laser powder directed energy deposition of Nb – Alloy C103 for thin wall geometries

This work focuses on the parameter development and microstructural characterization of Nb-based alloy C103 for thin wall structures produced via laser powder – directed energy deposition (LP – DED). Laser power and scanning speeds were varied as part of a design of experiments to identify adequate print parameters. Combinations were evaluated for relative density, porosity, and geometrical accuracy. A combination of a laser power of 1420 W and scanning speed of 14 mm/s resulted in a relative density >99%, exhibited a consistent weld bead profile and was used for further microstructural evaluation. A mix of optical and scanning electron microscopy (SEM) revealed small, slightly elongated grains along the edges and large epitaxial grains in the central region along the Build – Transverse view. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) analysis revealed Hf rich columnar cells in the center that transition into an evenly spaced cellular structure towards the edges of the built sample. Electron backscatter diffraction (EBSD) scans show a sharp [001] texture when looking at the cross section of the sample along the build direction. The Build – Scan view revealed a zig – zag pattern that follows the back – and – forth deposition strategy that was used. Finally, microhardness measurements were taken in the as – built (AB) and stress relieved (SR) conditions to baseline preliminary mechanical properties. The AB condition exhibited a large amount of scatter in the data and averages up to 11% larger than the SR condition. The reduction in scatter upon applying the SR cycle are indicative of a large concertation of dislocations present in the AB condition.

36 MATERIALS SCIENCE↗

NASA NTRS2002

Analytical Simulations of Energy-Absorbing Impact Spheres for a Mars Sample Return Earth Entry Vehicle

Nonlinear dynamic finite element simulations were performed to aid in the design of an energy-absorbing impact sphere for a passive Earth Entry Vehicle (EEV) that is a possible architecture for the Mars Sample Return (MSR) mission. The MSR EEV concept uses an entry capsule and energy-absorbing impact sphere designed to contain and limit the acceleration of collected samples during Earth impact without a parachute. The spherical shaped impact sphere is composed of solid hexagonal and pentagonal foam-filled cells with hybrid composite, graphite-epoxy/Kevlar cell walls. Collected Martian samples will fit inside a smaller spherical sample container at the center of the EEV's cellular structure. Comparisons were made of analytical results obtained using MSC.Dytran with test results obtained from impact tests performed at NASA Langley Research Center for impact velocities from 30 to 40 m/s. Acceleration, velocity, and deformation results compared well with the test results. The correlated finite element model was then used for simulations of various off-nominal impact scenarios. Off-nominal simulations at an impact velocity of 40 m/s included a rotated cellular structure impact onto a flat surface, a cellular structure impact onto an angled surface, and a cellular structure impact onto the corner of a step.

Billings, Marcus Dwight↗

NASA NTRS1999

Novel Approaches to Cellular Transplantation from the US Space Program

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

Pellis, Neal R.↗

DOE OSTI2025

Laser Powder Directed Energy Deposition of Steels for Nuclear Applications

This comprehensive investigation examines the structure–property relationships in two nuclear alloy systems—Alloy 709 (A709) austenitic stainless steel and Grade 92 (G-92) ferritic/martensitic (F/M) steel—manufactured via directed energy deposition (DED) for sodium-cooled fast reactor applications. This study establishes the fundamental mechanisms for controlling microstructures for optimizing the mechanical performance of additively manufactured nuclear materials through systematic heat treatment optimization and multiscale characterization. As-deposited A709 steel develops a complex multiscale strengthening architecture consisting of a fine cellular solidification structure with diameter of 2-3 µm within10–50 µm grains, elevated dislocation densities from rapid thermal cycling, and grain boundary precipitates that activate concurrent Hall–Petch, dislocation, and precipitation hardening mechanisms to achieve exceptional properties [yield strength (YS): 603 MPa, ultimate tensile strength (UTS): 844 MPa, Vickers hardness: 220 HV] that achieve a 44% superior strength compared to that of the wrought material. Heat treatments produce different results. Solution annealing (SA) dissolves the cellular structure and reduces the hardness to 190 HV. Precipitation treatment (PT) keeps the cellular structure but adds carbides, allowing the hardness to reach 205 HV. The best approach combines both treatments (SA+PT) and creates uniform precipitate distributions with M 23 C 6 carbides at the grain boundaries and MX carbonitrides in the matrix, achieving a hardness of 195 HV. However, directional differences persist, with a 12%–15% strength variation between orientations due to the inherited layered microstructural architecture that survives aggressive heat treatment. While tensile testing at 550°C demonstrates 40%–50% thermal softening with dynamic strain aging, DED A709 steel still maintains a 71% higher YS than that of the wrought material. Ion irradiation studies (100–400 dpa) of DED A709 steel reveal progressive radiation damage with increasing void density and radiation-induced segregation causing nickel enrichment and chromium depletion, which will ultimately compromise mechanical properties. As-deposited G-92 exhibits exceptional strength (UTS: 1650–1700 MPa, 430 HV) through a complex microstructure containing both ferrite and martensite phases, a high geometrically necessary dislocation (GND) density (17.04×10 14 /m 2 ), and fine carbides. Heat treatments create distinct changes. Normalizing produces fresh martensite with the highest hardness (460 HV) and an increased GND density (20.23×10 14 /m 2 ). Tempering develops dual precipitation systems and reduces the hardness to 290 HV. The optimal approach uses sequential normalizing plus tempering, achieving balanced properties with the lowest hardness (250 HV) and a reduced GND density (11.01×10 14 /m 2 ). A processing-dependent anisotropy is observed: horizontal specimens achieve superior ductile behavior, while vertical specimens exhibit brittle failure. A tempering heat treatment successfully mitigates this anisotropic behavior by transforming the hard martensitic as-deposited structure into tempered martensite enabling both horizontal and vertical specimens to exhibit similar stress–strain characteristics with visible necking behavior. Remarkably, testing at 550°C reveals a reversal in the anisotropy, where as-deposited specimens achieve near isotropy with superior thermal stability (a 15%–20% strength reduction), while tempered specimens develop an orientation dependence with a 25%–30% strength reduction. Both alloy systems demonstrate that DED processing creates specimens with a superior strength through refined microstructural features, though with distinct strengthening mechanisms—austenitic through cellular structures and precipitates versus F/M through phase transformations and precipitates. Heat treatment optimization requires alloy-specific approaches, with A709 benefiting from controlled precipitation while G-92 requires careful phase transformation control. The results show that DED manufacturing can produce nuclear materials with exceptional performance, but directional effects and temperature-dependent behavior must be carefully considered for reactor component design and qualification.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

NASA NTRS1990

A comparison of performance of lightweight mirrors

Four lightweight solid contoured back mirror shapes (a double arch, a single arch, a modified single arch, and a double concave mirror) and a cellular sandwich lightweight meniscus mirror, have been considered for the primary mirror of the Space Infrared Telescope Facility (SIRTF). A parametric design study using these shapes for the SIRTF 40 inch primary mirror with a focal ratio f/2 is presented. Evaluations of the optical performance and fundamental frequency analyses are performed to compare relative merits of each mirror configuration. Included in these are structural, optical, and frequency analyses for (1) different back contour shapes, (2) different number and location of the support points, and (3) two gravity orientations (ZENITH and HORIZON positions). The finite element program NASTRAN is used to obtain the structural deflections of the optical surface. For wavefront error analysis, FRINGE and PCFRINGE programs are used to evaluate the optical performance. A scaling law relating the optical and structural performance for various mirror contoured back shapes is developed.

Cho, Myung K.↗

DOE OSTI2024

Bacterial microcompartments as a next-generation metabolic engineering tool: utilizing nature's solution for confining challenging catabolic pathways

Advancements in synthetic biology have facilitated the incorporation of heterologous metabolic pathways into various bacterial chassis, leading to the synthesis of targeted bioproducts. However, total output from heterologous production pathways can suffer from low flux, enzyme promiscuity, formation of toxic intermediates, or intermediate loss to competing reactions, which ultimately hinder their full potential. The self-assembling, easy-to-modify, protein-based bacterial microcompartments (BMCs) offer a sophisticated way to overcome these obstacles by acting as an autonomous catalytic module decoupled from the cell's regulatory and metabolic networks. More than a decade of fundamental research on various types of BMCs, particularly structural studies of shells and their self-assembly, the recruitment of enzymes to BMC shell scaffolds, and the involvement of ancillary proteins such as transporters, regulators, and activating enzymes in the integration of BMCs into the cell's metabolism, has significantly moved the field forward. These advances have enabled bioengineers to design synthetic multi-enzyme BMCs to promote ethanol or hydrogen production, increase cellular polyphosphate levels, and convert glycerol to propanediol or formate to pyruvate. These pioneering efforts demonstrate the enormous potential of synthetic BMCs to encapsulate non-native multi-enzyme biochemical pathways for the synthesis of high-value products.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Volumetric imaging of the 3D orientation of cellular structures with a polarized fluorescence light-sheet microscope

Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations in biological samples, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the diffraction-limited three-dimensional distribution of the orientations and positions of ensembles of fluorescent dipoles that label biological structures. We share a set of visualization, histogram, and profiling tools for interpreting these positions and orientations. We model the distributions based on the polarization-dependent efficiency of excitation and detection of emitted fluorescence, using coarse-grained representations we call orientation distribution functions (ODFs). We apply ODFs to create physics-informed models of image formation with spatio-angular point-spread and transfer functions. We use theory and experiment to conclude that light-sheet tilting is a necessary part of our design for recovering all three-dimensional orientations. We use our system to extend known two-dimensional results to three dimensions in FM1-43-labeled giant unilamellar vesicles, fast-scarlet-labeled cellulose in xylem cells, and phalloidin-labeled actin in U2OS cells. Additionally, we observe phalloidin-labeled actin in mouse fibroblasts grown on grids of labeled nanowires and identify correlations between local actin alignment and global cell-scale orientation, indicating cellular coordination across length scales.

Science & Technology - Other Topics↗

DOE OSTI2023

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that WT MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1β, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1-NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.

MDGAs↗

DOE OSTI2021

Substrate Partitioning into Protein Macromolecular Frameworks for Enhanced Catalytic Turnover

Spatial partitioning of chemical processes is an important attribute of many biological systems, the effect of which is reflected in the high efficiency of enzymes found within otherwise chaotic cellular environments. Barriers, often provided through the formation of compartments or phase segregation, gate the access of macromolecules and small molecules within the cell and provide an added level of metabolic control. Taking inspiration from nature, we have designed virus-like particles (VLPs) as nanoreactor compartments that sequester enzyme catalysts and have used these as building blocks to construct 3D protein macromolecular framework (PMF) materials, which are structurally characterized using small-angle X-ray scattering (SAXS). Additionally, the highly charged PMFs form a separate phase in suspension, and by tuning the ionic strength, we show positively charged molecules preferentially partition into the PMF, while negatively charged molecules are excluded. This molecular partitioning was exploited to tune the catalytic activity of enzymes enclosed within the individual particles in the PMF, the results of which showed that positively charged substrates had turnover rates that were 8500× faster than their negatively charged counterparts. Moreover, the catalytic PMF led to cooperative behavior resulting in charge dependent trends opposite to those observed with individual P22 nanoreactor particles.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRS2012

Joining and Assembly of Bulk Metallic Glass Composites Through Capacitive Discharge

Bulk metallic glasses (BMGs), a class of amorphous metals defined as having a thickness greater than 1 mm, are being broadly investigated by NASA for use in spacecraft hardware. Their unique properties, attained from their non-crystalline structure, motivate several game-changing aerospace applications. BMGs have low melting temperatures so they can be cheaply and repeatedly cast into complex net shapes, such as mirrors or electronic casings. They are extremely strong and wear-resistant, which motivates their use in gears and bearings. Amorphous metal coatings are hard, corrosion-resistant, and have high reflectivity. BMG composites, reinforced with soft second phases, can be fabricated into energy-absorbing cellular panels for orbital debris shielding. One limitation of BMG materials is their inability to be welded, bonded, brazed, or fastened in a convenient method to form larger structures. Cellular structures (which can be classified as trusses, foams, honeycombs, egg boxes, etc.) are useful for many NASA, commercial, and military aerospace applications, including low-density paneling and shields. Although conventional cellular structures exhibit high specific strength, their porous structures make them challenging to fabricate. In particular, metal cellular structures are extremely difficult to fabricate due to their high processing temperatures. Aluminum honeycomb sandwich panels, for example, are used widely as spacecraft shields due to their low density and ease of fabrication, but suffer from low strength. A desirable metal cellular structure is one with high strength, combined with low density and simple fabrication. The thermoplastic joining process described here allows for the fabrication of monolithic BMG truss-like structures that are 90% porous and have no heat-affected zone, weld, bond, or braze. This is accomplished by welding the nodes of stacked BMG composite panels using a localized capacitor discharge, forming a single monolithic structure. This removes many complicated and costly fabrication steps. Moreover, the cellular structures detailed in this work are among the highest- strength and most energy-absorbent materials known. This implies that a fabricated structure made from these materials would have unequaled mechanical properties compared to other metal foams or trusses. The process works by taking advantage of the electrical properties of the matrix material in the metal-matrix composite, which in this case is a metallic glass. Due to the random nanoscale arrangement of atoms (without any grain boundaries), the matrix glass exhibits a near-constant electrical resistivity as a function of temperature. By placing the composite panels between two copper electrode plates and discharging a capacitor, the entire matrix of the panel can be heated to approximately 700 C in 10 milliseconds, which is above the alloy s solidus but below the liquidus. By designing the geometry of the panels into the shape of an egg box, the electrical discharge localizes only in the tips of each pyramidal cell. By applying a forging load during discharge, the nodes of the panels can be fused together into a single piece, which then dissipates heat through radiation back into a glassy state. This means that two panels can be metallurgically fused into one panel with no heat-affected zone, creating a seamless connection between panels. During the process, the soft metal particles (dendrites) that are uniformly distributed in the glassy matrix to increase the toughness are completely unaffected by the thermoplastic joining. The novelty is that a truss (or foam-like) structure can be formed with excellent energy- absorbing capabilities without the need for machining. The technique allows for large-scale fabrication of panels, well-suited for spacecraft shields or military vehicle door panels. Crystalline metal cellular structures cannot be fabricated using the thermoplastic joining technique described here. If metal panels were te assembled into a cellular structure, they would either have to be welded, brazed, bonded, or fastened together, creating a weak spot in the structure at each connection. Welded parts require a welding material to be added to the joint and exhibit a soft and weak heat-affected zone. Brazing and bonding do not form a metallurgical joint and thus exhibit low strengths, especially when the panels are pulled apart and fasteners require high-stress-concentration holes to be drilled. No equivalent rapid heating method exists for assembling metal panels together into cellular structures, and thus, those parts must be foamed, machined, or investment cast if they are to form a monolithic structure. If the crystalline panels were to be joined using capacitive discharge, as with a spot welder, their bond would be very weak, and the panels would have to be extremely thin. In contrast, the strength of joined BMG parts has been demonstrated to have strength comparable to the parent material. This technique opens up the possibility of using large-scale BMG hardware in spacecraft, military, or commercial applications.

Hofmann, Douglas C.↗