Engineering topics
Publications and source records attributed to Daily, Michael D..
Disclosed herein are monomer embodiments that can be used to make polymers, such as homopolymers, heteropolymers, and that can be used in particular embodiments to make sequence-defined polymers. Also disclosed herein are methods of making polymers using such monomer embodiments. Methods of using the polymers disclosed herein also are described.
Monomer embodiments that can be used to make polymers, such as homopolymers, heteropolymers, and that can be used in particular embodiments to make sequence-defined polymers are described. Also described are methods of making polymers using such monomer embodiments. Methods of using the polymers also are described.
Two-dimensional (2D) materials with molecular-scale thickness have attracted increasing interest for separation, electronic, catalytic, optical, energy and biomedical applications. Although extensive research on 2D materials, such as graphene and graphene oxide, has been performed in recent years, progress is limited on self-assembly of 2D materials from sequence-specific macromolecules, especially from synthetic sequences that could exhibit lipid-like self-assembly of bilayer sheets and mimic membrane proteins for functions. The creation of such new class of materials could enable development of highly stable biomimetic membranes that exhibit cell-membrane-like molecular transport with exceptional selectively and high transport rates. Here we demonstrate self-assembly of lipid-like 12-mer peptoids into extremely stable, crystalline, flexible and free-standing 2D membrane materials. As with cell membranes, upon exposure to external stimuli, these materials exhibit changes in thickness, varying from 3.5 nm to 5.6 nm. We find that self-assembly occurs through a facile crystallization process, in which inter-peptoid hydrogen bonds and enhanced hydrophobic interactions drive the formation of a highly-ordered structure. Molecular simulation confirms this is the energetically favored structure. Displaying functional groups at arbitrary locations of membrane-forming peptoids produces membranes with similar structures. This research further shows that single-layer membranes can be coated onto substrate surfaces. Moreover, membranes with mechanically-induced defects can self-repair. Given that peptoids are sequence-specific and exhibit protein-like molecular recognition with enhanced stability, we anticipate our membranes to be a robust platform tailored to specific applications.
Protein self-assembly is a commonplace phenomenon in living systems and is frequently responsible for building molecular machines that carry out the vast array of functions, such as molecular separation and selective ion transport. Inspired by in nature, various proteins and peptides have been designed and exploited for self-assembly of functional materials in vitro. However, the application of these protein- and peptide-based materials is limited because of their poor stabilities against thermal and chemical degradation. Therefore, there is a great need to develop protein-like synthetic polymers that can function like proteins and peptides for molecular recognition and self-assembly, but exhibit high stabilities. There are several known chemical systems that can create non-natural, sequence-specific polymers, such as ?-peptides and peptoids (poly-N-substituted glycines). Peptoids have received particular attention because they can be cheaply and efficiently synthesized, and several hundred commercially available amines can be used to build their large side-chain diversity. We recently demonstrated that peptoids were able to mimic peptides commonly present in natural biominerals for unprecedented control over both calcite morphology and growth kinetics. In this presentation, we report our progress in exploiting peptoids to mimic proteins and peptides for self-assembly. Specifically, we demonstrate that 12-mer peptoids are able to self-assemble into highly-ordered membrane-like materials both in solution and on substrate surfaces. In aqueous solution, these peptoids self-assemble into highly-crystalline and free-floating nanosheets through a solvent-driven crystallization process. These nanosheets have single-bilayer thickness (3.2 nm) and large area (up to mm2). X-ray diffraction data indicate that these peptoids are highly packed through p-p stacking and peptoid side-chain hydrogen bonding. These results represent the smallest peptoid oligomers that self-assemble into free-floating nanosheets and do not require the compression of monolayers formed at the water-air interface. The formation of single-bilayer-thick nanosheets also occurs on various substrate surfaces. For example, on freshly-cleaved mica surface, we observed that nanosheets were formed through a heterogeneous nucleation process. Similar nanosheets were assembled even when 12-mer peptoids were specifically conjugated with functional groups, indicating that self-assembly of 12-mer peptoids into nanosheets is robust, and these nanosheets can serve as a well-defined 2D platform for post-functionalization. Peptoid self-assembly is highly sequence-specific, and pH sensitive. When the diblock-like 12-mer peptoids are switched to an alternative motif, the resulting 12-mers only self-assemble into fiber-like materials. Multi-scale simulations are also used to provide insights into peptoid-assembly mechanisms
Monomer embodiments that can be used to make polymers, such as homopolymers, heteropolymers, and that can be used in particular embodiments to make sequence-defined polymers are described. Also described are methods of making polymers using such monomer embodiments. Methods of using the polymers also are described.
The description of peptides and the use of molecular dynamics simulations to refine structures and investigate the dynamics on an atomistic scale are well developed. Through a consensus in this community over multiple decades, parameters were developed for molecular interactions that only require the sequence of amino-acids and an initial guess for the three-dimensional structure. The recent discovery of peptoids will require a retooling of the currently available interaction potentials in order to have the same level of confidence in the predicted structures and pathways as there is presently in the peptide counterparts. Here we present modeling of peptoids using a combination of ab initio molecular dynamics (AIMD) and atomistic resolution classical forcefield (FF) to span the relevant time and length scales. To properly account for the dominant forces that stabilize ordered structures of peptoids, namely steric-, electrostatic, and hydrophobic interactions mediated through sidechain-sidechain interactions in the FF model, those have to be first mapped out using high fidelity atomistic representations. A key feature here is not only to use gas phase quantum chemistry tools, but also account for solvation effects in the condensed phase through AIMD. One major challenge is to elucidate ion binding to charged or polar regions of the peptoid and its concomitant role in the creation of local order. Here, similar to proteins, a specific ion effect is observed suggesting that both the net charge and the precise chemical nature of the ion will need to be described. MDD was supported by MS3 (Materials Synthesis and Simulation Across Scales) Initiative at Pacific Northwest National Laboratory. Research was funded by the Laboratory Directed Research and Development program at Pacific Northwest National Laboratory. MDB acknowledges support from US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Material & Engineering. CJM acknowledges support from US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. PNNL is a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy.
Abstract Sequence control in polymers, well‐known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence‐defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H‐bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence‐defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen‐bonding motifs, and will thus enable new macromolecules and materials with useful functions.
Abstract Sequence control in polymers, well‐known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence‐defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H‐bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence‐defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen‐bonding motifs, and will thus enable new macromolecules and materials with useful functions.
We demonstrate the accuracy and effectiveness of a Lagrangian particle-based method, smoothed particle hydrodynamics (SPH), to study diffusion in biomolecular systems by numerically solving the time-dependent Smoluchowski equation for continuum diffusion. The numerical method is first verified in simple systems and then applied to the calculation of ligand binding to an acetylcholinesterase monomer. Unlike previous studies, a reactive Robin boundary condition (BC), rather than the absolute absorbing (Dirichlet) boundary condition, is considered on the reactive boundaries. This new boundary condition treatment allows for the analysis of enzymes with "imperfect" reaction rates. Rates for inhibitor binding to mAChE are calculated at various ionic strengths and compared with experiment and other numerical methods. We find that imposition of the Robin BC improves agreement between calculated and experimental reaction rates. Although this initial application focuses on a single monomer system, our new method provides a framework to explore broader applications of SPH in larger-scale biomolecular complexes by taking advantage of its Lagrangian particle-based nature.