Unconventional mechanical and thermal behaviours of MOF CALF-20.

CALF-20 was recently identified as a benchmark sorbent for CO2 capture at the industrial scale, however comprehensive atomistic insight into its mechanical/thermal properties under working conditions is still lacking. In this study, we developed a general-purpose machine-learned potential (MLP) for the CALF-20 MOF framework that predicts the thermodynamic and mechanical properties of the structure at finite temperatures within first-principles accuracy. Interestingly, CALF-20 was demonstrated to exhibit both negative area compression and negative thermal expansion. Most strikingly, upon application of the tensile strain along the [001] direction, CALF-20 was shown to display a distinct two-step elastic deformation behaviour, unlike typical MOFs that undergo plastic deformation after elasticity. Furthermore, this MOF was shown to exhibit a fracture strain of up to 27% along the [001] direction at room temperature comparable to that of MOF glasses. These abnormal thermal and mechanical properties make CALF-20 as attractive material for flexible and stretchable electronics and sensors.

Design of Mixed-Matrix MOF Membranes with Asymmetric Filler Density and Intrinsic MOF/Polymer Compatibility for Enhanced Molecular Sieving.

The separation of high-value-added chemicals from organic solvents is important for many industries. Membrane-based nanofiltration offers a more energy-efficient separation than the conventional thermal processes. Conceivably, mixed-matrix membranes (MMMs), encompassing metal-organic frameworks (MOFs) as fillers, are poised to promote selective separation via molecular sieving, synergistically combining polymers flexibility and fine-tuned porosity of MOFs. Nevertheless, conventional direct mixing of MOFs with polymer solutions results in underutilization of the MOF fillers owing to their uniform cross-sectional distribution. Therefore, in this work, a multizoning technique is proposed to produce MMMs with an asymmetric-filler density, in which the MOF fillers are distributed only on the surface of the membrane, and a seamless interface at the nanoscale. The design strategy demonstrates five times higher MOF surface coverage, which results in a solvent permeance five times higher than that of conventional MMMs while maintaining high selectivity. Practically, MOFs are paired with polymers of similar chemical nature to enhance their adhesion without the need for surface modification. The approach offers permanently accessible MOF porosity, which translates to effective molecular sieving, as exemplified by the polybenzimidazole and Zr-BI-fcu-MOF system. The findings pave the way for the development of composite materials with a seamless interface.

Microscopic insight into the shaping of MOFs and its impact on CO2 capture performance.

The traditional synthesis method produces microcrystalline powdered MOFs, which prevents direct implementation in real-world applications which demand strict control of shape, morphology and physical properties. Therefore, shaping of MOFs via the use of binders is of paramount interest for their practical use in gas adsorption/separation, catalysis, sensors, etc. However, so far, the binders have been mostly selected by trial-and-error without anticipating the adhesion between the MOF and binder components to ensure the processability of homogeneous and mechanically stable shaped MOFs and the impact of the shaping on the intrinsic properties of the MOFs has been overlooked. Herein, we deliver a first systematic multiscale computational exploration of MOF/binder composites by selecting CALF-20, a prototypical MOF for real application in the field of CO2 capture, and a series of binders that cover a rather broad spectrum of properties in terms of rigidity/flexibility, porosity, and chemical functionality. The adhesion between the two components and hence the effectiveness of the shaping as well as the impact of the overall porosity of the CALF-20/binder on the CO2/N2 selectivity, CO2 sorption capacity and kinetics was analyzed. Shaping of CALF-20 by carboxymethyl cellulose was predicted to enable a fair compromise between excellent adhesion between the two components, whilst maintaining high CO2/N2 selectivity, large CO2 uptake and CO2 transport as fast as in the CALF-20. This multiscale computational tool paves the way towards the selection of an appropriate binder to achieve an optimum shaping of a given MOF in terms of processability whilst maintaining its high level of performance.

Mechanistic insight into the structure, thermodynamics and dynamics of equilibrium gels of multi-armed DNA nanostars.

The unique sequence specificity rule of DNA makes it an ideal molecular building block for constructing periodic arrays and devices with nanoscale accuracy and precision. Here, we present the self-assembly of DNA nanostars having three, four and five arms into a gel phase using a simplistic coarse-grained bead-spring model developed by Z. Xing, C. Ness, D. Frenkel and E. Eiser (Macromolecules, 2019, 52, 504-512). Our simulations show that the DNA nanostars form a thermodynamically stable fully bonded gel phase from an unstructured liquid phase with the lowering of temperature. We characterize the phase transition by calculating several structural features such as the radial distribution function and structure factor. The thermodynamics of gelation is quantified by the potential energy and translational pair-entropy of the system. The phase transition from an arrested gel phase to an unstructured liquid phase has been modelled using a two-state theoretical model. We find that this transition is enthalpy driven, and loss of configuration and translational entropy is counterpoised by enthalpic interaction of the DNA sticky-ends, which gives rise to a gel phase at low temperature. The absolute rotational and translational entropy of the systems, measured using a two-phase thermodynamic model, also substantiates the gel transition. The slowing down of the dynamics upon approaching the transition temperature from a high temperature demonstrates the phase transition to a gel phase. A detailed numerical simulation study of the morphology, dynamics and thermodynamics of DNA gelation can provide guidance for future experiments, is easily extensible to other polymeric systems, and is expected to help in understanding the physics of self-assembly.

Molecular Rectifiers with a Very High Rectification Ratio Enabled by Oxidative Damage in Double-Stranded DNA.

In this work, we report a novel strategy to construct highly efficient molecular diodes using oxidatively damaged DNA molecules. Being exposed to several endogenous and exogenous events, DNA suffers from constant oxidative damage, leading to the oxidation of guanine to 8-oxoguanine (8oxoG). Here, we study the charge migration properties of native and oxidatively damaged DNA using a multiscale multiconfigurational methodology comprising molecular dynamics, density functional theory, and kinetic Monte Carlo simulations. We perform a comprehensive study to understand the effect of different concentrations and locations of 8oxoG in a dsDNA sequence on its charge-transport properties and find tunable rectifier properties having potential applications in molecular electronics such as molecular switches and molecular rectifiers. We also discover the negative differential resistance properties of the fully oxidized Drew-Dickerson sequence. The presence of 8oxoG guanine leads to the trapping of charge, thus operating as a charge sink, which reveals how oxidized guanine saves the rest of the genome from further oxidative damage.

Graphene oxide as a dual template for induced helicity of peptides.

Artificial template-mediated fabrication of secondary structures within peptides always attracts great interest in biological systems due to several biomimetic interactions. In all earlier studies, a uniform template containing molecules/nanomaterials was used to target only one type of peptide at a time, which extensively limits the diversity in the generation of artificial protein surface/binding sites. This limitation can be overcome by the incorporation of more than one binding template (heterogeneity) in a single system, for example, Janus nanomaterials, which are challenging and difficult to synthesize. In this context, graphene oxide (GO) is considered an artificial binding site (template). It contains two distinctive binding zones, i.e., surface and edge, which can induce the secondary structure of peptides based on complementary interactions. To establish our concept, we have implemented a hybrid sequence i.e., i, i + 4, i + 7 and i + 11 pattern peptides, which defines a more linear surface, suitable for recognition by the two-dimensional GO. Depending on the amino acid residue at the specific locations, we observed substantial enhancement of peptide helicity either at the surface or at the edges of GO from the random coil. However, non-interacting peptides remain as a random coil. We have established this by circular dichroism study at various conditions, as well as atomic force microscopy and optical imaging study. Furthermore, we have also established our observations using molecular dynamics (MD) simulations. This study reveals that the synthesized GO-peptides composite with different secondary structures and recognition residues can mimic biological systems.

Ultra-high permeable phenine nanotube membranes for water desalination.

Nanopore desalination technology hinges on high water-permeable membranes which, at the same time, block ions efficiently. In this study, we consider a recently synthesized [Science363, 151-155 (2019)] phenine nanotube (PNT) for water desalination applications. Using both equilibrium and non-equilibrium molecular dynamics simulations, we show that the PNT membrane completely rejects salts, but permeates water at a rate which is an order-of-magnitude higher than that of all the membranes used for water filtration. We provide the microscopic mechanisms of salt rejection and fast water-transport by calculating the free-energy landscapes and electrostatic potential profiles. A collective diffusion model accurately predicts the water permeability obtained from the simulations over a wide range of pressure gradients. We propose a method to calculate the osmotic water permeability from the equilibrium simulation data and find that it is very high for the PNT membrane. These remarkable properties of PNT can be applied in various nanofluidic applications, such as ion-selective channels, ionic transistors, sensing, molecular sieving, and blue energy harvesting.

Nanoscale structures and mechanics of peptide nucleic acids.

Peptide nucleic acids (PNAs) are charge-neutral polyamide oligomers having extremely favorable thermal stability and high affinity to cell membranes when coupled with cationic cell-penetrating peptides (CPPs), as well as the encouraging antisense and antigene activity in cell-free systems. The study of the mechanical properties of short PNA molecules is rare both in experiments and theoretical calculations. Here, we studied the microscopic structures and elastic properties; namely, persistence length, stretch modulus, twist-stretch coupling, and structural crookedness of double-stranded PNA (dsPNA) and their hybrid derivatives using all-atom MD simulation and compared them with those of double-stranded DNA (dsDNA) and double-stranded RNA (dsRNA). The stretch modulus of the dsPNA is found to be ∼160 pN, an order of magnitude lower than that of dsDNA and smaller than dsRNA, respectively. Similarly, the persistence length of dsPNA is found to be ∼35 nm, significantly smaller than those of dsDNA and dsRNA. The PNA-DNA and PNA-RNA hybrid duplexes have elastic properties lying between that of dsPNA and dsDNA/dsRNA. We argue that the neutral backbones of the PNA make it less stiff than dsDNA and dsRNA molecules. Measurement of structural crookedness and principal component analysis additionally support the bending flexibility of dsPNA. Detailed analysis of the helical-rise coupled to helical-twist indicates that the PNA-DNA hybrid over-winds like dsDNA, while PNA-PNA and PNA-RNA unwind like dsRNA upon stretching. Because of the highly flexible nature of PNA, it can bind other biomolecules by adopting a wide range of conformations and is believed to be crucial for future nanobiotechnology research studies.

Designer DNA Hydrogels Stimulate 3D Cell Invasion by Enhanced Receptor Expression and Membrane Endocytosis.

DNA has emerged as one of the smartest biopolymers to bridge the gap between chemical science and biology to design scaffolds like hydrogels by physical entanglement or chemical bonding with remarkable properties. We present here a completely new application of DNA-based hydrogels in terms of their capacity to stimulate membrane endocytosis, leading to enhanced cell spreading and invasion for cells in ex vivo 3D spheroids models. Multiscale simulation studies along with DLS data showed that the hydrogel formation was enhanced at lower temperature and it converts to liquid with increase in temperature. DNA hydrogels induced cell spreading as observed by the increase in cellular area by almost two-fold followed by an increase in the receptor expression, the endocytosis, and the 3D invasion potential of migrating cells. Our first results lay the foundation for upcoming diverse applications of hydrogels to probe and program various cellular and physiological processes that can have lasting applications in stem cell programming and regenerative therapeutics.

Mechanistic insights into the effects of key mutations on SARS-CoV-2 RBD-ACE2 binding.

Some recent SARS-CoV-2 variants appear to have increased transmissibility compared to the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on the target cells and infect them. In this study, we provide atomic-level insights into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities for the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than for the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.

Mechanical properties of DNA and DNA nanostructures: comparison of atomistic, Martini and oxDNA models.

The flexibility and stiffness of small DNA molecules play a fundamental role ranging from several biophysical processes to nano-technological applications. Here, we estimate the mechanical properties of short double-stranded DNA (dsDNA) with lengths ranging from 12 base-pairs (bp) to 56 bp, paranemic crossover (PX) DNA and hexagonal DNA nanotubes (DNTs) using two widely used coarse-grained models - Martini and oxDNA. To calculate the persistence length (Lp) and the stretch modulus (γ) of the dsDNA, we incorporate the worm-like chain and elastic rod model, while for the DNTs, we implement our previously developed theoretical framework. We compare and contrast all of the results with previously reported all-atom molecular dynamics (MD) simulations and experimental results. The mechanical properties of dsDNA (Lp ∼ 50 nm, γ ∼ 800-1500 pN), PX DNA (γ ∼ 1600-2000 pN) and DNTs (Lp ∼ 1-10 µm, γ ∼ 6000-8000 pN) estimated using the Martini soft elastic network and oxDNA are in very good agreement with the all-atom MD and experimental values, while the stiff elastic network Martini reproduces values of Lp and γ which are an order of magnitude higher. The high flexibility of small dsDNA is also depicted in our calculations. However, Martini models proved inadequate to capture the salt concentration effects on the mechanical properties with increasing salt molarity. oxDNA captures the salt concentration effect on the small dsDNA mechanics. But it is found to be ineffective for reproducing the salt-dependent mechanical properties of DNTs. Also, unlike Martini, the time evolved PX DNA and DNT structures from the oxDNA models are comparable to the all-atom MD simulated structures. Our findings provide a route to study the mechanical properties of DNA and DNA based nanostructures with increased time and length scales and has a remarkable implication in the context of DNA nanotechnology.

What do we know about DNA mechanics so far?

The DNA molecule, apart from carrying the genetic information, plays a crucial role in a variety of biological processes and finds applications in drug design, nanotechnology and nanoelectronics. The molecule undergoes significant structural transitions under the influence of forces due to physiological and non-physiological environments. Here, we summarize the insights gained from simulations and single-molecule experiments on the structural transitions and mechanics of DNA under force, as well as its elastic properties, in various environmental conditions, and discuss appealing future directions.

Liquid crystal ordering of nucleic acids.

Several analytical calculations and computer simulations propose that cylindrical monodispersive rods having an aspect ratio (ratio of length to diameter) greater than 4 can exhibit liquid crystal (LC) ordering. But, recent experiments demonstrated the signature of LC ordering in systems of 4- to 20-base pair (bp) long nucleic acids (NAs) that do not satisfy the shape anisotropy criterion. Mechanisms of end-to-end adhesion and stacking have been proposed to explain this phenomenon. In this study, using all-atom molecular dynamics (MD) simulation, we explicitly verify the end-to-end stacking of double-stranded RNA (dsRNA) and demonstrate the LC ordering at the microscopic level. Using umbrella sampling (US) calculation, we quantify the potential of mean force (PMF) between two dsRNAs for various reaction coordinates (RCs) and compare our results with previously reported PMFs for double-stranded DNA (dsDNA). The PMF profiles demonstrate the anisotropic nature of inter-NA interaction. We find that, like dsDNA, dsRNA also prefers to stack on top of each other while repelling sideways, leading to the formation of supra-molecular-columns that undergo LC ordering at high NA volume fraction (φ). We also demonstrate and quantify the nematic ordering of the RNAs using several hundred nanosecond-long MD simulations that remain almost invariant for different initial configurations and under different external physiological conditions.

Atomic structures of RNA nanotubes and their comparison with DNA nanotubes.

We present a computational framework to model RNA based nanostructures and study their microscopic structures. We model hexagonal nanotubes made of 6 dsRNA (RNTs) connected by double crossover (DX) at different positions. Using several hundred nano-second (ns) long all-atom molecular dynamics simulations, we study the atomic structure, conformational change and elastic properties of RNTs in the presence of explicit water and ions. Based on several structural quantities such as root mean square deviation (RMSD) and root mean square fluctuation (RMSF), we find that the RNTs are almost as stable as DNA nanotubes (DNTs). Although the central portion of the RNTs maintain its cylindrical shape, both the terminal regions open up to give rise to a gating like behavior which can play a crucial role in drug delivery. From the bending angle distribution, we observe that the RNTs are more flexible than DNTs. The calculated persistence length of the RNTs is in the micron range which is an order of magnitude higher than that of a single dsRNA. The stretch modulus of the RNTs from the contour length distribution is in the range of 4-7 nN depending on the sequence. The calculated persistence length and stretch modulus are in the same range of values as in the case of DNTs. To understand the structural properties of RNTs at the individual base-pair level we have also calculated all the helicoidal parameters and analyzed the relative flexibility and rigidity of RNTs having a different sequence. These findings emphasized the fascinating properties of RNTs which will expedite further theoretical and experimental studies in this field.