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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.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Distribution and Spectroscopy of Green Fluorescent Protein and Acyl-CoA: Cholesterol Acytransferase in Sf21 Insect Cells

Acyl-CoA: cholesterol acyltransferase (ACAT) is thought to significantly participate in the pathway of cholesterol esterification that underlies the pathology of artherosclerosis. This enzyme is a membrane protein known to be preferentially bound within the endoplasmic reticulum of mammalian cells, from which location it esterifies cholesterol derived from low density lipoprotein. Cultures of insect cells were separately infected with baculovirus containing the gene for green fluroescent protein (GFP) and with baculovirus containing tandem genes for GFP and ACAT. These infected cultures expressed GFP and the fusion protein GCAT, respectively, with maximum expression occurring on the fourth day after infection. Extraction of GFP- and of GCAT-expressing cells with urea and detergent resulted in recovery of fluorescent protein in aqueous solution. Fluorescence spectra at neutral pH were identical for both GFP and GCAT extracts in aqueous solution, indicating unperturbed tertiary structure for the GFP moiety within GCAT. In a cholesterol esterification assay, GCAT demonstrated ACAT activity, but with less efficiency compared to native ACAT. It was hypothesized that the membrane protein ACAT would lead to differences in localization of GCAT compared to GFP within the respective expressing insect cells. The GFP marker directly and also within the fusion protein GCAT was accordingly used as the intracellular probe that was fluorescently analyzed by the new biophotonics technique of hyperspectral imaging. In that technique, fluorescence imaging was obtained from two dimensional arrays of cells, and regions of interest from within those images were then retrospectively analyzed for the emission spectra that comprises the image. Results of hyperspectral imaging of insect cells on day 4 postinfection showed that GCAT was preferentially localized to the cytoplasm of these cells compared to GFP. Furthermore, the emission spectra obtained for the localized GCAT displayed a peak blue shift from 518nm obtained in neutral aqueous solution to 505nm obtained in localized regions within the cells. This blue shift indicates change in the fluorescence coupling of the GFP moiety of GCAT. It is hypothesized that change in tertiary environment of GCAT, coincident with intracellular deposition of GCAT, follows from intracellular trafficking of GCAT leading to membrane interactions with the ACAT moiety, and/or self-assembly of GCAT, that alters the chromophore environment of the GFP moiety of GCAT. These findings introduce a new technique of biophotonic imaging to studies of intracellular protein trafficking and interactions. This technique of hyperspectral imaging could contribute to advancing the emergent field of proteomics. Because of the noninvasive nature of this technique, kinetic processes associated with intracellular protein trafficking, and interactions of proteins within cellular domains, can be considered for investigation within a single cell as well as a cell population.

Richmond, R. C.↗
NASA NTRS2005

The Future of Bio-technology

Hosts of technologies, most notably in electronics, have been on the path of miniaturization for decades and in 2005 they have crossed the threshold of the nano-scale. Crossing the nano-scale threshold is a milestone in miniaturization, setting impressive new standards for component-packing densities. It also brings technology to a scale at which quantum effects and fault tolerance play significant roles and approaches the feasible physical limit form many conventional "top-down" manufacturing methods. I will suggest that the most formidable manufacturing problems in nanotechnology will be overcome and major breakthroughs will occur in a host of technologies, when nanotechnology converges with bio-technology; i.e. I will argue that the future of bio-technology is in nanotechnology. In 2005, methods in molecular biology, microscopy, bioinformatics, biochemistry, and genetic engineering have focused considerable attention on the nano-scale. On this scale, biology is a kind of recursive chemistry in which molecular recognition, self-assembly, self-organization and self-referencing context-control lead to the emergence of the complexity of structures and processes that are fundamental to all life forms. While we are still far from understanding this complexity, we are on the threshold of being able to use at least some of these biological properties for .technology. I will discuss the use of biomolecules, such as DNA, RNA, and proteins as "tools" for the bio-technologist of the future. More specifically, I will present in some detail an example of how we are using a genetically engineered 60-kDa protein (HSP60) from an organism living in near boiling sulfuric acid to build nano-scale templates for arranging metallic nanoparticles. These "extremophile" HSP60s self-assemble into robust double-ring structures called "chaperonins," which further assemble into filaments and arrays with nanometer accuracy. I will discuss our efforts to use chaperonins to organize quantum dots, electronic and magnetic nano-particles for electronic and photonic applications.

Trent, Jonathan↗
DOE OSTI2025

Rare Earth Element-Induced Condensation of the Block V of the Repeats-in-Toxin Domain from CyaA from Bordetella pertussis for Separations

Rare earth elements (REEs) are critical for the development of a range of new technologies. However, the current industrial separation processes of these metals from natural sources, recycled materials, and industrial effluents involve the large consumption of organic solvents, resulting in a sizable environmental footprint. We aim to exploit the high affinity of the block V peptide of the repeats-in-toxin (RTX) domain of the adenylate cyclase protein from Bordetella pertussis for the separation of REEs. This peptide selectively binds with lanthanide (Ln) cations and can undergo Ln-induced phase separation, which can be used in bioseparation processes. Here, we evaluated the self-assembling structures of complexes of the RTX domain peptide folded in the presence of Ln 3+ cations. Size distribution and surface potential measurements of complexes were taken to understand the Ln-induced changes in the complexed peptide. Transmission electron microscopy imaging was used to explore the structures of complexes, while anomalous small-angle X-ray scattering measurements were used to determine the distribution of Ln 3+ ions within the protein-based macrostructures. In the presence of excess Ln 3+ , we observed the formation of coral-like cylindrical structures comprised of Ln 3+ -RTX complexes, with approximately eight trivalent metals per peptide within the nanosized assemblies. These findings provide new insights into the structural organization of assembled RTX domains and their ability to coordinate with REEs, forming nanosized, metal-rich structures that naturally condense, providing a proof-of-concept for protein-based separation processes of these critical materials.

chemical structure↗
NASA NTRS2019

Emergence of Simple Ion Channels by Self-Assembly of Short Peptides

As protocells transitioned from structures bound by membranes made of simple amphiphiles, such as fatty acids, to structures containing phospholipid membranes, they became nearly impermeable to charged species. Yet, the ability to transport ions across membranes was vital to regulating cellular volume, pH homeostasis, generating energy and sensing the environment. For this reason, life evolved ion channels, protein structures surrounding water-filled pores in the membrane that facilitated ion transport. In contemporary cells, ion channels are complex protein assemblies. Could the same function be carried out, even if less efficiently and selectively, by much simpler peptides at the origins of life? To answer this question, we turned to trichogen (GAIV), an 11-residue peptide that was found to permeabilize membrane, causing leakage of the vesicle content including ions. Since GAIV is synthesized non-gnomically, it represents as excellent model for the earliest, poorly optimized channels. Understanding the mechanism by which short peptides, such as GAIV, mediate ion transport across membranes provides crucial information on the emergence, structure and the mechanism of action of the earliest ion channels. In this study, we used extensive molecular dynamics (MD) simulations to investigate directly spontaneous assembly of GAIV peptide and its structural dynamics, the formation of an induced water pore across the membrane and consequently ion conduction through the membrane.

Wei, Chenyu↗
DOE OSTI2025

Reweighting configurations generated by transferable, machine learned models for protein sidechain backmapping

Multiscale modeling requires the linking of models at different levels of detail, with the goal of gaining accelerations from lower fidelity models while recovering fine details from higher resolution models. Communication across resolutions is particularly important in modeling soft matter, where tight couplings exist between molecular-level details and mesoscale structures. While multiscale modeling of biomolecules has become a critical component in exploring their structure and self-assembly, backmapping from coarse-grained to fine-grained, or atomistic, representations presents a challenge, despite recent advances through machine learning. A major hurdle, especially for strategies utilizing machine learning, is that backmappings can only approximately recover the atomistic ensemble of interest. We demonstrate conditions for which backmapped configurations may be reweighted to exactly recover the desired atomistic ensemble. By training separate decoding models for each sidechain type, we develop an algorithm based on normalizing flows and geometric algebra attention to autoregressively propose backmapped configurations for any protein sequence. Critical for reweighting with modern protein force fields, our trained models include all hydrogen atoms in the backmapping and make probabilities associated with atomistic configurations directly accessible. We also demonstrate, however, that reweighting is extremely challenging despite state-of-the-art performance on recently developed metrics and generation of configurations with low energies in atomistic protein force fields. Through detailed analysis of configurational weights, we show that machine-learned backmappings must not only generate configurations with reasonable energies, but also correctly assign relative probabilities under the generative model. These are broadly important considerations in generative modeling of atomistic molecular configurations.

Monroe, Jacob I. [Univ. of Arkansas, Fayetteville,↗
DOE OSTI2025

Mediation of Colloidal Encounter Dynamics by Surface Roughness

Rigorous understanding on the self-assembly of colloidal nanocrystals is crucial to develop tailored nanostructured materials for energy storage, sensing, and optical fields. Despite extensive studies on the self-assembly, a mechanistic understanding of self-assembly under an external field still remains an ongoing challenge. Here, in this work, we used optical tweezers that impose an external attractive force field, resulting in the self-assembly of alpha-phase sodium yttrium fluoride nanocrystals. The dynamic force that is strongly dependent on the surface roughness of the nanocrystals is shown to be a decisive factor for a direct contact between the nanocrystals, manifested by the roughness-dependent hydrodynamic resistivity and Langevin dynamic simulations. Our study provides direct evidence that the role of dynamics is equally important in understanding the self-assembly, which has been rarely observed in the self-assembly in contrast with many studies on the equilibrium forces. These results may have further impact in other fields, such as having explanatory power for the probability of nonclassical crystal growth or the structure of viral spike proteins that affect the probability of viruses binding with cells.

Felsted, Robert G. [Univ. of Washington, Seattle, ↗
DOE OSTI2025

Abbr. Final report: Self-assembled molecular containers as artificial water channels: towards biomimetic desalination membranes

Global water scarcity demands advances in desalination technologies that can deliver more fresh water with less energy. Current reverse osmosis membranes are fundamentally limited by a trade-off between how much water they can pass and how well they block salts. To address this challenge, we developed a bottom-up strategy to design and test artificial water channels that mimic the efficiency of biological proteins but are built from robust synthetic molecules. Over two years, we synthesized and evaluated more than twenty molecular channel candidates, including supramolecular macrocycles and nanographene pores with atomically precise structures. We showed that small chemical modifications allow direct control over pore size and chemistry, which in turn govern water permeability and salt rejection. In collaboration with university partners, we reported the first experimental demonstration of water transport through a nanographene pore, bridging a long-standing gap between simulation and experiment. Several of the artificial channels we developed achieved water–salt selectivity beyond conventional polymer membranes, highlighting their potential for next-generation desalination and precision separations.

36 MATERIALS SCIENCE↗
NASA NTRS2000

Fluorescence Studies of Protein Crystal Nucleation

One of the most powerful and versatile methods for studying molecules in solution is fluorescence. Crystallization typically takes place in a concentrated solution environment, whereas fluorescence typically has an upper concentration limit of approximately 1 x 10(exp -5)M, thus intrinsic fluorescence cannot be employed, but a fluorescent probe must be added to a sub population of the molecules. However the fluorescent species cannot interfere with the self-assembly process. This can be achieved with macromolecules, where fluorescent probes can be covalently attached to a sub population of molecules that are subsequently used to track the system as a whole. We are using fluorescence resonance energy transfer (FRET) to study the initial solution phase self-assembly process of tetragonal lysozyme crystal nucleation, using covalent fluorescent derivatives which crystallize in the characteristic P432121 space group. FRET studies are being carried out between cascade blue (CB-lys, donor, Ex 376 nm, Em 420 nm) and lucifer yellow (LY-lys, acceptor, Ex 425 nm, Em 520 nm) asp101 derivatives. The estimated R0 for this probe pair, the distance where 50% of the donor energy is transferred to the acceptor, is approximately 1.2 nm, compared to 2.2 nm between the side chain carboxyls of adjacent asp101's in the crystalline 43 helix. The short CB-lys lifetime (approximately 5 ns), coupled with the large average distances between the molecules ((sup 3) 50 nm) in solution, ensure that any energy transfer observed is not due to random diffusive interactions. Addition of LY-lys to CB-lys results in the appearance of a second, shorter lifetime (approximately 0.2 ns). Results from these and other ongoing studies will be discussed in conjunction with a model for how tetragonal lysozyme crystals nucleate and grow, and the relevance of that model to microgravity protein crystal growth

Pusey, Marc L.↗
DOE OSTI2026

Peptoid-Based Nanosheets Exhibiting Broad Antiviral Activity Against Enveloped RNA Viruses

Enveloped RNA viruses, such as Influenza A (H1N1) and Sindbis virus, pose persistent global health threats due to their high mutation rates, efficient transmission, and frequent drug resistance. By mimicking host cell membrane receptors, multivalent virus inhibitors can block viral attachment, making them promising broad-spectrum antiviral agents. However, most of existing antivirals are often limited by strain specificity, short-lived efficacy, and toxicity. Here, we introduce a broad-spectrum antiviral platform based on highly tunable and biocompatible two-dimensional nanomembranes (2DNMs) self-assembled from amphiphilic peptoids, operating via a non-genomic, mutation-insensitive mechanism. By varying peptoid sequence, we design and synthesize over twenty different 2DNMs with various surface charge and high density of viral-attachment ligands (VALs). The self-assembled architecture of these stable 2DNMs provides cooperative noncovalent multivalent binding to virus particles that result in effective inhibition of viral infection. Screening of variants identified three leads that potently suppressed Influenza A (H1N1) and Sindbis virus infection across median tissue culture infectious dose (TCID50), plaque, RT–qPCR, and immunofluorescence assays, while maintaining >90% cell viability. These nanosheets significantly reduced infectious titers, viral RNA replication, and intracellular viral protein expression, indicating inhibition at early stages of viral entry and propagation. The sequence programmability, chemical robustness, and mutation-insensitive antiviral activity distinguish 2DNMs from traditional antivirals and positions them as a versatile materials platform for antiviral coatings, protective barriers, and prophylactic biomedical applications.

Influenza A virus↗
NASA NTRS2003

The Building Blocks of Materials: Gathering Knowledge at the Molecular Level

Two start-up positions were created within SD46 to pursue developments in the rapidly expanding areas of biomineralization and nano-technology. As envisioned by Dr. Sandor Lehoczy, the new laboratories to be developed must have the capacity to investigate not only processes associated with the self-assembly of molecules but also the examination of self-assembled structures. For these purposes, laboratories capable of performing the intended function, particularly light scattering spectroscopy and atomic force microscopy were created. What follows then are recent advances arising from the development of these new laboratories. With the implementation of the Atomic Force Microscopy Facility, examples of investigations that determine a correlation between the molecular structure of materials and their macroscopic physical properties are provided. In addition, examples of investigations with particular emphasis on the physical properties of protein crystals, at the molecular level, and subsequent macroscopic characteristics are as provided. Finally, progress in fabrication of technology at the nano-scale levels at the developmental stage is also presented.

Source record↗
DOE OSTI2026

Excipient screening by lyophilization provides insights into spray drying formulations for nanoparticle vaccines

Nanoparticles have shown great promise as delivery platforms in the development of tunable and safe vaccines. Nanolipoprotein particles (NLPs), also known as nanodiscs, are discoidal nanoparticles composed of a lipid bilayer stabilized at their periphery by apolipoproteins. Under the right conditions, the NLP self-assembly process is highly customizable in terms of lipids and apolipoprotein constituents, allowing for tunable physical and chemical characteristics. This flexibility allows a wide range of vaccine antigens and adjuvants to be incorporated onto the NLP platform for tailored vaccine design. The stability of NLPs during long term storage is a very important factor in developing a vaccine delivery platform suitable for widespread global use. When stored in a solution for extended periods of time, NLPs dissociate into their corresponding lipids and protein constituents, leading to particle degradation. Proper stabilization of NLPs can often be achieved by lyophilization (i.e. freeze-drying), a method widely used for various applications including pharmaceuticals. This process, however, can be damaging to particles without the presence of lyoprotectants or excipients that help maintain particle stability during lyophilization. Another method used to stabilize vaccines and pharmaceuticals is spray drying, a process that converts liquid formulations into dry powders through controlled heating and airflow. While spray drying is rapid, scalable, and cost-effective, lyophilization is typically a gentler process that better retains biomolecule structure and function. Both processes use excipients for particle stabilization, so lyophilization can be used as a surrogate to test stability of NLPs, to down-select formulations that may withstand the harsher conditions of spray drying. To screen different formulations, NLPs were synthesized and purified to homogeneity by size exclusion chromatography (SEC) and samples were prepared with a wide range of lyoprotectants and/or excipients. To assess the protective effects of excipients on NLPs upon spray drying, both pre- and post-lyophilized samples were analyzed by SEC. To assess the protective effects upon heating (encountered during the spray drying process), NLP samples were incubated at elevated temperatures prior to SEC analysis. The lyoprotectants and excipients evaluated in this study had different efficiencies in protecting NLPs during lyophilization and heating tests. Trehalose, for example, exhibits stabilization on NLPs both upon lyophilization and heating whereas leucine accelerated NLP dissociation. Although some lyoprotectants are effective by themselves, different combinations can decrease the stabilization of NLPs. Shelf-stable vaccines that do not require cold-chain storage are essential for global accessibility and our findings provide fundamental insight into how to advance NLP-based vaccines for these applications.

Serrano, Litzay J [Lawrence Livermore National Lab↗
NASA NTRS2000

Fluorescence Studies of Protein Crystal Nucleation

We have postulated that, in the case of tetragonal chicken egg white lysozyme, crystal growth occurs by the addition of pre-critical nuclei sized n-mers that form in the bulk solution, and that the n-mer growth units were multiples of the tetrameric 4(sub 3) helical structure. These have the strongest intermolecular bonds in the crystal and are therefore likely to be the first species formed. High resolution AFM studies provide strong supporting evidence for this model, but the data also suggest that the actual species in solution may not be identical in structure to that found in the crystal. We are using fluorescence resonance energy transfer (FRET) to study the initial solution phase self-assembly process, using covalent fluorescent derivatives which crystallize in the characteristic P4(sub 3)2(sub 1)2(sub 1) space group. FRET studies are being carried out between the cascade blue (CB-lys, donor, Ex(sub max) 366 nm, Em 420 nm) and lucifer yellow (LY-lys, acceptor, Ex(sub max) 430 nm, Em 528 nm) asp101 derivatives. The estimated R(sub 0) for this probe pair, the distance where 50% of the donor energy is transferred to the acceptor, is approx. 1.2 nm, compared to 2.2 nm between the side chain carboxyls of adjacent asp101's in the crystalline 4(sub 3) helix. The short donor lifetime of 2.80 ns (chi(sup 2) = 0.644), coupled with the large average distances between the molecules (greater than or equal to 50 nm) in solution, ensure that any energy transfer observed is not due to random diffusive interactions. Lifetime data show that CB-lys has a single lifetime when it is the only species in solution. Similarly, LY-lys also exhibits a single lifetime of 4.63 ns (chi(sup 2) = 0.42) when alone in solution. Addition of LY-lys to CB-lys results in the appearance of a third lifetime component of 0.348ns for the CB-lys. The fractional intensities of the different species present can be used to estimate the distribution of monomer and n-mers in solution. The self-association process is a function of the protein concentration relative to the saturation concentration, and observing it in dilute solution (conc. less than or equal to 10(exp -5)M) requires that the experiments be performed under low solubility conditions, i.e., low temperatures and high salt concentrations. Data from preliminary steady state FRET studies with N-terminal bound pyrene acetic acid (PAA-lys, donor, Ex 340 nm, Em 376 nm) and asp101 LY-lys as an acceptor showed a consistent trend of decreasing donor fluorescence intensity with increasing total protein concentration. The FRET data have been obtained at pH 4.6, 0.1M NaAc buffer, at 5 and 7% NaCl, 4 C. The corresponding C(sub sat) values are 0.471 and 0.362 mg/ml (approx. 3.3 and approx. 2.5 x 10(exp -5)M respectively). The donor fluorescence decrease is more pronounced at7% NaCl, consistent with the expected increased intermolecular interactions at higher salt concentrations as reflected in the lower solubility. Results from these and other ongoing studies will be discussed in conjunction with an emerging model for how tetragonal lysozyme crystals nucleate and the relevance of that model to other proteins.

Pusey, Marc↗
NASA NTRS2006

Computer Modeling of Protocellular Functions: Peptide Insertion in Membranes

Lipid vesicles became the precursors to protocells by acquiring the capabilities needed to survive and reproduce. These include transport of ions, nutrients and waste products across cell walls and capture of energy and its conversion into a chemically usable form. In modem organisms these functions are carried out by membrane-bound proteins (about 30% of the genome codes for this kind of proteins). A number of properties of alpha-helical peptides suggest that their associations are excellent candidates for protobiological precursors of proteins. In particular, some simple a-helical peptides can aggregate spontaneously and form functional channels. This process can be described conceptually by a three-step thermodynamic cycle: 1 - folding of helices at the water-membrane interface, 2 - helix insertion into the lipid bilayer and 3 - specific interactions of these helices that result in functional tertiary structures. Although a crucial step, helix insertion has not been adequately studied because of the insolubility and aggregation of hydrophobic peptides. In this work, we use computer simulation methods (Molecular Dynamics) to characterize the energetics of helix insertion and we discuss its importance in an evolutionary context. Specifically, helices could self-assemble only if their interactions were sufficiently strong to compensate the unfavorable Free Energy of insertion of individual helices into membranes, providing a selection mechanism for protobiological evolution.

Rodriquez-Gomez, D.↗
NASA NTRS2001

Fabrication of poly(ethylene glycol) hydrogel microstructures using photolithography

The fabrication of hydrogel microstructures based upon poly(ethylene glycol) diacrylates, dimethacrylates, and tetraacrylates patterned photolithographically on silicon or glass substrates is described. A silicon/silicon dioxide surface was treated with 3-(trichlorosilyl)propyl methacrylate to form a self-assembled monolayer (SAM) with pendant acrylate groups. The SAM presence on the surface was verified using ellipsometry and time-of-flight secondary ion mass spectrometry. A solution containing an acrylated or methacrylated poly(ethylene glycol) derivative and a photoinitiator (2,2-dimethoxy-2-phenylacetophenone) was spin-coated onto the treated substrate, exposed to 365 nm ultraviolet light through a photomask, and developed with either toluene, water, or supercritical CO2. As a result of this process, three-dimensional, cross-linked PEG hydrogel microstructures were immobilized on the surface. Diameters of cylindrical array members were varied from 600 to 7 micrometers by the use of different photomasks, while height varied from 3 to 12 micrometers, depending on the molecular weight of the PEG macromer. In the case of 7 micrometers diameter elements, as many as 400 elements were reproducibly generated in a 1 mm2 square pattern. The resultant hydrogel patterns were hydrated for as long as 3 weeks without delamination from the substrate. In addition, micropatterning of different molecular weights of PEG was demonstrated. Arrays of hydrogel disks containing an immobilized protein conjugated to a pH sensitive fluorophore were also prepared. The pH sensitivity of the gel-immobilized dye was similar to that in an aqueous buffer, and no leaching of the dye-labeled protein from the hydrogel microstructure was observed over a 1 week period. Changes in fluorescence were also observed for immobilized fluorophore labeled acetylcholine esterase upon the addition of acetyl acholine.

NASA Discipline Life Sciences Technologies↗
DOE OSTI2025

Functional Design of Peptide Materials Based on Supramolecular Cohesion

Peptide materials offer a broad platform to design biomimetic soft matter, and filamentous networks that emulate those in extracellular matrices and the cytoskeleton are among the important targets. Given the vast sequence space, a combination of computational approaches and readily accessible experimental techniques is required to design peptide materials efficiently. Here, we report here on a strategy that utilizes this combination to predict supramolecular cohesion within filaments of peptide amphiphiles, a property recently linked to supramolecular dynamics and consequently bioactivity. Using established coarse-grained simulations on 10,000 randomly generated peptide sequences, we identified 3500 likely to self-assemble in water into nanoscale filaments. Atomistic simulations of small clusters were used to further analyze this subset of sequences and identify mathematical descriptors that are predictive of intermolecular cohesion, which was the main purpose of this work. We arbitrarily selected a small cohort of these sequences for chemical synthesis and verified their fiber morphology. With further characterization, we were able to link the latent heat associated with fiber to micelle transitions, an indicator of cohesion and potential supramolecular dynamicity within the filaments, to calculated hydrogen bond densities in the simulation clusters. Based on validation from in situ synchrotron X-ray scattering and differential scanning calorimetry, we conclude that the phase transitions can be easily observed by very simple polarized light microscopy experiments. We are encouraged by the methodology explored here as a relatively low-cost and fast way to design potential functions of peptide materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Amino Acid Sequence Controls Enhanced Electron Transport in Heme-Binding Peptide Monolayers

Metal-binding proteins have the exceptional ability to facilitate long-range electron transport in nature. Despite recent progress, the sequence-structure–function relationships governing electron transport in heme-binding peptides and protein assemblies are not yet fully understood. In this work, the electronic properties of a series of heme-binding peptides inspired by cytochrome bc1 are studied using a combination of molecular electronics experiments, molecular modeling, and simulation. Self-assembled monolayers (SAMs) are prepared using sequence-defined heme-binding peptides capable of forming helical secondary structures. Following monolayer formation, the structural properties and chemical composition of assembled peptides are determined using atomic force microscopy and X-ray photoelectron spectroscopy, and the electronic properties (current density–voltage response) are characterized using a soft contact liquid metal electrode method based on eutectic gallium–indium alloys (EGaIn). Our results show a substantial 1000-fold increase in current density across SAM junctions upon addition of heme compared to identical peptide sequences in the absence of heme, while maintaining a constant junction thickness. These findings show that amino acid composition and sequence directly control enhancements in electron transport in heme-binding peptides. Overall, this study demonstrates the potential of using sequence-defined synthetic peptides inspired by nature as functional bioelectronic materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Cryo-EM Visualization of Intermolecular π-Electron Interactions within π-Conjugated Peptidic Supramolecular Polymers

The self-assembly of “π-peptides” – molecules with π-electron cores substituted with two or more oligopeptide chains – brings organic electronic function into biologically relevant nanomaterials. π-Peptides assemble into fibrillar nanomaterials as driven by enthalpic peptide-based hydrogen bonding networks and pi-core-based quadrupolar interactions. A large body of spectroscopic, morphological and computational studies informs on the nature of the self-assembly process and the resulting nanostructures, but detailed structural information has remained elusive. Here, inspired by the recent use of cryogenic electron microscopy (cryo-EM) to provide high-resolution structures for synthetic peptide nanomaterials, we present here the use of cryo-EM to offer ca. 3 Å resolution of π-peptide nanomaterial assemblies, visualizing for the first time the nature of the intermolecular π-core electronic interactions responsible for energy transport through these supramolecular materials.

Group theory↗
DOE OSTI2026

Substrate-Directed Dimensional and Phase Control of Peptide Assemblies on Two-Dimensional van der Waals Materials

Understanding and controlling biomolecular self-assembly on van der Waals (vdW) materials has the potential to advance hybrid bioelectronic devices by enabling precise tuning of the interface and modulation of the resulting electronic properties of the biomolecule-vdW heterostructure. However, how surface properties of vdW materials direct biomolecule assembly remains poorly understood. To fill this knowledge gap, we investigated the assembly of a peptide known to assemble into two-dimensional (2D) crystalline films on MoS 2 on three representative vdW surfaces: WS 2 , MoS 2 , and highly oriented pyrolytic graphite (HOPG). Using in situ atomic force microscopy (AFM), we find that assembly is substrate-dependent, resulting in multilayers on WS 2 , monolayers on MoS 2 , and multiple coexisting phases on HOPG. WS 2 exhibits a higher negative charge, strong long-range electrostatic interactions, and extensive hydration layering that may promote multilayer stacking. In contrast, MoS 2 has stronger short-range interactions with the peptides but much weaker long-range interactions and hydration structure, which may favor monolayer formation. Molecular dynamics simulations predict a corresponding switch from monolayer to multilayer aggregates of the adsorbed monomers, reflected in their relative mobilities. On hydrophobic HOPG, the peptides bind most strongly and remain as monomers with high surface mobility. The peptide dimers comprising the basic unit of the crystals are more compact on HOPG, which has a smaller lattice constant than WS 2 or MoS 2 , suggesting strain contributes to stabilizing multiple phases. Our results provide mechanistic insights into how surface charge and hydration structure, and the lattice structure of the substrates governs peptide assembly on vdW materials, offering a framework to rationally control the 2D peptide-vdW heterostructures.

Molecular dynamics simulations↗