Scattering evidence of positional charge correlations in polyelectrolyte complexes.

Polyelectrolyte complexation plays an important role in materials science and biology. The internal structure of the resultant polyelectrolyte complex (PEC) phase dictates properties such as physical state, response to external stimuli, and dynamics. Small-angle scattering experiments with X-rays and neutrons have revealed structural similarities between PECs and semidilute solutions of neutral polymers, where the total scattering function exhibits an Ornstein-Zernike form. In spite of consensus among different theoretical predictions, the existence of positional correlations between polyanion and polycation charges has not been confirmed experimentally. Here, we present small-angle neutron scattering profiles where the polycation scattering length density is matched to that of the solvent to extract positional correlations among anionic monomers. The polyanion scattering functions exhibit a peak at the inverse polymer screening radius of Coulomb interactions, q* ≈ 0.2 Å-1. This peak, attributed to Coulomb repulsions between the fragments of polyanions and their attractions to polycations, is even more pronounced in the calculated charge scattering function that quantifies positional correlations of all polymer charges within the PEC. Screening of electrostatic interactions by adding salt leads to the gradual disappearance of this correlation peak, and the scattering functions regain an Ornstein-Zernike form. Experimental scattering results are consistent with those calculated from the random phase approximation, a scaling analysis, and molecular simulations.

Measuring response functions of active materials from data.

From flocks of birds to biomolecular assemblies, systems in which many individual components independently consume energy to perform mechanical work exhibit a wide array of striking behaviors. Methods to quantify the dynamics of these so-called active systems generally aim to extract important length or time scales from experimental fields. Because such methods focus on extracting scalar values, they do not wring maximal information from experimental data. We introduce a method to overcome these limitations. We extend the framework of correlation functions by taking into account the internal headings of displacement fields. The functions we construct represent the material response to specific types of active perturbation within the system. Utilizing these response functions we query the material response of disparate active systems composed of actin filaments and myosin motors, from model fluids to living cells. We show we can extract critical length scales from the turbulent flows of an active nematic, anticipate contractility in an active gel, distinguish viscous from viscoelastic dissipation, and even differentiate modes of contractility in living cells. These examples underscore the vast utility of this method which measures response functions from experimental observations of complex active systems.

Nonequilibrium statistical thermodynamics of multicomponent interfaces.

Nonequilibrium interfacial thermodynamics has important implications for crucial biological, physical, and industrial-scale transport processes. Here, we discuss a theory of local equilibrium for multiphase multicomponent interfaces that builds upon the "sharp" interface concept first introduced by Gibbs, allowing for a description of nonequilibrium interfacial processes such as those arising in evaporation, condensation, adsorption, etc. By requiring that the thermodynamics be insensitive to the precise location of the dividing surface, one can identify conditions for local equilibrium and develop methods for measuring the values of intensive variables at the interface. We then use extensive, high-precision nonequilibrium molecular dynamics (NEMD) simulations to verify the theory and establish the validity of the local equilibrium hypothesis. In particular, we demonstrate that equilibrium equations of state are also valid out of equilibrium, and can be used to determine interfacial temperature and chemical potential(s) that are consistent with nonequilibrium generalizations of the Clapeyron and Gibbs adsorption equations. We also show, for example, that, far from equilibrium, temperature or chemical potential differences need not be uniform across an interface and may instead exhibit pronounced discontinuities. However, even in these circumstances, we demonstrate that the local equilibrium hypothesis and its implications remain valid. These results provide a thermodynamic foundation and computational tools for studying or revisiting a wide variety of interfacial transport phenomena.

High-efficiency stretchable light-emitting polymers from thermally activated delayed fluorescence.

Stretchable light-emitting materials are the key components for realizing skin-like displays and optical biostimulation. All the stretchable emitters reported to date, to the best of our knowledge, have been based on electroluminescent polymers that only harness singlet excitons, limiting their theoretical quantum yield to 25%. Here we present a design concept for imparting stretchability onto electroluminescent polymers that can harness all the excitons through thermally activated delayed fluorescence, thereby reaching a near-unity theoretical quantum yield. We show that our design strategy of inserting flexible, linear units into a polymer backbone can substantially increase the mechanical stretchability without affecting the underlying electroluminescent processes. As a result, our synthesized polymer achieves a stretchability of 125%, with an external quantum efficiency of 10%. Furthermore, we demonstrate a fully stretchable organic light-emitting diode, confirming that the proposed stretchable thermally activated delayed fluorescence polymers provide a path towards simultaneously achieving desirable electroluminescent and mechanical characteristics, including high efficiency, brightness, switching speed and stretchability as well as low driving voltage.

Synthetic and Computational Design Insights toward Mimicking Protein Binding of Phosphate.

The unique and precise capabilities of proteins are renowned for their specificity and range of application. Effective mimicking of protein-binding offers enticing potential to direct their abilities toward useful applications, but it is nevertheless quite difficult to realize this characteristic of protein behavior in a synthetic material. Here, we design, synthesize, and evaluate experimentally and computationally a series of multicomponent phosphate-binding peptide amphiphile micelles to derive design insights into how protein binding behavior translates to synthetic materials. By inserting the Walker A P-loop binding motif into this peptide synthetic material, we successfully implemented the protein-binding design parameters of hydrogen-bonding and electrostatic interaction to bind phosphate completely and selectively in this highly tunable synthetic platform. Moreover, in this densely arrayed peptide environment, we use molecular dynamics simulations to identify an intriguing mechanistic shift of binding that is inaccessible in traditional proteins, introducing two corresponding new design elements─flexibility and minimization of the loss of entropy due to ion binding, in protein-analogous synthetic materials. We then translate these new design factors to de novo peptide sequences that bind phosphate independent of protein-extracted sequence or conformation. Overall, this work reveals that traditional complex conformational restrictions of binding by proteins can be replaced and repurposed in a multicomponent peptide amphiphile synthetic material, opening up opportunities for future enhanced protein-inspired design.

Control of liquid crystals combining surface acoustic waves, nematic flows, and microfluidic confinement.

The optical properties of liquid crystals serve as the basis for display, diagnostic, and sensing technologies. Such properties are generally controlled by relying on electric fields. In this work, we investigate the effects of microfluidic flows and acoustic fields on the molecular orientation and the corresponding optical response of nematic liquid crystals. Several previously unknown structures are identified, which are rationalized in terms of a state diagram as a function of the strengths of the flow and the acoustic field. The new structures are interpreted by relying on calculations with a free energy functional expressed in terms of the tensorial order parameter, using continuum theory simulations in the Landau-de Gennes framework. Taken together, the findings presented here offer promise for the development of new systems based on combinations of sound, flow, and confinement.

Machine learning active-nematic hydrodynamics.

Hydrodynamic theories effectively describe many-body systems out of equilibrium in terms of a few macroscopic parameters. However, such parameters are difficult to determine from microscopic information. Seldom is this challenge more apparent than in active matter, where the hydrodynamic parameters are in fact fields that encode the distribution of energy-injecting microscopic components. Here, we use active nematics to demonstrate that neural networks can map out the spatiotemporal variation of multiple hydrodynamic parameters and forecast the chaotic dynamics of these systems. We analyze biofilament/molecular-motor experiments with microtubule/kinesin and actin/myosin complexes as computer vision problems. Our algorithms can determine how activity and elastic moduli change as a function of space and time, as well as adenosine triphosphate (ATP) or motor concentration. The only input needed is the orientation of the biofilaments and not the coupled velocity field which is harder to access in experiments. We can also forecast the evolution of these chaotic many-body systems solely from image sequences of their past using a combination of autoencoders and recurrent neural networks with residual architecture. In realistic experimental setups for which the initial conditions are not perfectly known, our physics-inspired machine-learning algorithms can surpass deterministic simulations. Our study paves the way for artificial-intelligence characterization and control of coupled chaotic fields in diverse physical and biological systems, even in the absence of knowledge of the underlying dynamics.

Molecular analysis of the type III interferon complex and its applications in protein engineering.

Type III interferons (IFNλs) are cytokines with critical roles in the immune system and are attractive therapeutic candidates due to their tissue-specific activity. Despite entering several clinical trials, results have demonstrated limited efficacy and potency, partially attributed to low-affinity protein-protein interactions (PPIs) responsible for receptor complex formation. Subsequently, structural studies of the native IFNλ signaling complexes remain inaccessible. While protein engineering can overcome affinity limitations, tools to investigate low-affinity systems like these remain limited. To provide insights into previous efforts to strengthen the PPIs within this complex, we perform a molecular analysis of the extracellular ternary complexes of IFNλ3 using both computational and experimental approaches. We first use molecular simulations and modeling to quantify differences in PPIs and residue strain fluctuations, generate detailed free energy landscapes, and reveal structural differences between an engineered, high-affinity complex, and a model of the wild-type, low-affinity complex. This analysis illuminates distinct behaviors of these ligands, yielding mechanistic insights into IFNλ complex formation. We then apply these computational techniques in protein engineering and design by utilizing simulation data to identify hotspots of interaction to rationally engineer the native cytokine-receptor complex for increased stability. These simulations are then validated by experimental techniques, showing that a single mutation at a computationally predicted site of interaction between the two receptors increases PPIs and improves complex formation for all IFNλs. This study highlights the power of molecular dynamics simulations for protein engineering and design as applied to the IFNλ family but also presents a potential tool for analysis and engineering of other systems with low-affinity PPIs.

Optimized design of block copolymers with covarying properties for nanolithography.

The ability to impart multiple covarying properties into a single material represents a grand challenge in manufacturing. In the design of block copolymers (BCPs) for directed self-assembly and nanolithography, materials often balance orthogonal properties to meet constraints related to processing, structure and defectivity. Although iterative synthesis strategies deliver BCPs with attractive properties, identifying materials with all the required attributes has been difficult. Here we report a high-throughput synthesis and characterization platform for the discovery and optimization of BCPs with A-block-(B-random-C) architectures for lithographic patterning in semiconductor manufacturing. Starting from a parent BCP and using thiol-epoxy 'click' chemistry, we synthesize a library of BCPs that cover a large and complex parameter space. This allows us to readily identify feature-size-dependent BCP chemistries for 8-20-nm-pitch patterns. These blocks have similar surface energies for directed self-assembly, and control over the segregation strength to optimize the structure (favoured at higher segregation strengths) and defectivity (favoured at lower segregation strengths).

Minimal Model of Solitons in Nematic Liquid Crystals.

Solitons in liquid crystals have generated considerable interest. Several hypotheses of varying complexity have been advanced to explain how they arise, but consensus has not emerged yet about the underlying forces responsible for their formation or their structure. In this work, we present a minimal model for solitons in achiral nematic liquid crystals, which reveals the key requirements needed to generate them in the absence of added charges. These include a surface inhomogeneity, consisting of an adsorbed particle capable of producing a twist, flexoelectricity, dielectric contrast, and an applied ac electric field that can couple to the director's orientation. Our proposed model is based on a tensorial representation of a confined liquid crystal, and it predicts the formation of "butterfly" structures, quadrupolar in character, in regions of a slit channel where the director is twisted by the surface imperfection. As the applied electric field is increased, solitons (or "bullets") become detached from the wings of the butterfly, and then propagate rapidly throughout the system. The main observations that emerge from the model, including the formation and structure of butterflies, bullets, and stripes, as well as the role of surface inhomogeneity and the strength of the applied field, are consistent with experimental findings presented here for nematic LCs confined between two chemically treated parallel plates.

Structural and Mechanical Response of Two-Component Photoswitchable Lipid Bilayer Vesicles.

Optical control of phospholipids is an attractive option for the rapid, reversible, and tunable manipulation of membrane structure and dynamics. Azo-PC, a lipid with an azobenzene group within one acyl chain, undergoes a light-induced trans-to-cis isomerization and thus arises as a powerful tool for manipulating lipid order and dynamics. Here, we report on vesicle-scale micropipette measurements and atomistic simulations to probe the elastic stretching modulus, water permeability, toughness, thickness, and membrane area upon isomerization. We investigated both dynamics and steady-state properties. In pure azo-PC membranes, we found that the molecular area in trans was 16% smaller than that in cis, the membrane's stretching modulus kA was 2.5 ± 0.3 times greater, and the water permeability PW was 3.5 ± 0.5 times smaller. We also studied mixtures of azo-PC with the miscible, unsaturated lipid DOPC. Atomistic molecular dynamics simulations show how the membrane thickness, chain order, and correlations across membrane leaflets explain the experimental data. Together, these data show how one rotating bond changes the molecular- and membrane-scale properties. These results will be useful for photopharmacology and for developing new materials whose permeability, elasticity, and toughness may be switched on demand.

Curvature and confinement effects on chiral liquid crystal morphologies.

Chiral liquid crystals (ChLCs) exhibit an inherent twist that originates at the molecular scale and can extend over multiple length scales when unconstrained. Under confinement, the twist is thwarted, leading to formation of defects in the molecular order that offer distinct optical responses and opportunities for colloidal driven assembly. Past studies have explored spheroidal confinement down to the nanoscopic regime, where curved boundaries produce surface defects to accommodate topological constraints and restrict the propagation of cuboidal defect networks. Similarly, strict confinement in channels and shells has been shown to give rise to escaped configurations and skyrmions. However, little is known about the role of extrinsic curvature in the development of cholesteric textures and Blue Phases (BP). In this paper, we examine the palette of morphologies that arises when ChLCs are confined in toroidal and cylindrical cavities. The equilibrium morphologies are obtained following an annealing strategy of a Landau-de Gennes free energy functional. Three dimensionless groups are identified to build phase diagrams: the natural twist, the ratio of elastic energies, and the circumscription of a BP cell. Curvature is shown to introduce helical features that are first observed as a Double Twist, and progress to Chiral Ribbons and, ultimately, Helical BP and BP. Chiral ribbons are examined as useful candidates for driven assembly given their tunability and robustness.

Advanced Materials for Energy-Water Systems: The Central Role of Water/Solid Interfaces in Adsorption, Reactivity, and Transport.

The structure, chemistry, and charge of interfaces between materials and aqueous fluids play a central role in determining properties and performance of numerous water systems. Sensors, membranes, sorbents, and heterogeneous catalysts almost uniformly rely on specific interactions between their surfaces and components dissolved or suspended in the water-and often the water molecules themselves-to detect and mitigate contaminants. Deleterious processes in these systems such as fouling, scaling (inorganic deposits), and corrosion are also governed by interfacial phenomena. Despite the importance of these interfaces, much remains to be learned about their multiscale interactions. Developing a deeper understanding of the molecular- and mesoscale phenomena at water/solid interfaces will be essential to driving innovation to address grand challenges in supplying sufficient fit-for-purpose water in the future. In this Review, we examine the current state of knowledge surrounding adsorption, reactivity, and transport in several key classes of water/solid interfaces, drawing on a synergistic combination of theory, simulation, and experiments, and provide an outlook for prioritizing strategic research directions.

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity.

Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib's mechanism of Mpro inhibition. To improve the inhibitory efficiency and to increase the ligand selectivity for the viral target, we determined the minimal portion of the molecule (fragment) that is responsible for most of the interactions that arise within the masitinib-Mpro complex. We found that masitinib forms highly stable and specific H-bond interactions with Mpro through its pyridine and aminothiazole rings. Importantly, the interaction with His163 is a key anchoring point of the inhibitor, and its perturbation leads to ligand unbinding within nanoseconds. Based on these observations, a small library of rationally designed masitinib derivatives (M1-M5) was proposed. Our results show increased inhibitory efficiency and highly reduced cytotoxicity for the M3 and M4 derivatives compared to masitinib.

Strongly Chiral Liquid Crystals in Nanoemulsions.

Liquid crystal (LC) emulsions represent a class of confined soft matter that exhibit exotic internal organizations and size-dependent properties, including responses to chemical and physical stimuli. Past studies have explored micrometer-scale LC emulsion droplets but little is known about LC ordering within submicrometer-sized droplets. This paper reports experiments and simulations that unmask the consequences of confinement in nanoemulsions on strongly chiral LCs that form bulk cholesteric and blue phases (BPs). A method based on light scattering is developed to characterize phase transitions of LCs within the nanodroplets. For droplets with a radius to the pitch ratio (Rv /p0 ) as small as 2/3, the BP-to-cholesteric transition is substantially suppressed, leading to a threefold increase of the BP temperature interval relative to bulk behavior. Complementary simulations align with experimental findings and reveal the dominant role of chiral elastic energy. For Rv /p0  ≈ 1/3, a single LC phase forms below the clearing point, with simulations revealing the new configuration to contain a τ-1/2 disclination that extends across the nanodroplet. These findings are discussed in the context of mechanisms by which polymer networks stabilize BPs and, more broadly, for the design of nanoconfined soft matter.

Parameter estimation for X-ray scattering analysis with Hamiltonian Markov Chain Monte Carlo.

Bayesian-inference-based approaches, in particular the random-walk Markov Chain Monte Carlo (MCMC) method, have received much attention recently for X-ray scattering analysis. Hamiltonian MCMC, a state-of-the-art development in the field of MCMC, has become popular in recent years. It utilizes Hamiltonian dynamics for indirect but much more efficient drawings of the model parameters. We described the principle of the Hamiltonian MCMC for inversion problems in X-ray scattering analysis by estimating high-dimensional models for several motivating scenarios in small-angle X-ray scattering, reflectivity, and X-ray fluorescence holography. Hamiltonian MCMC with appropriate preconditioning can deliver superior performance over the random-walk MCMC, and thus can be used as an efficient tool for the statistical analysis of the parameter distributions, as well as model predictions and confidence analysis.

Spatiotemporal control of liquid crystal structure and dynamics through activity patterning.

Active materials are capable of converting free energy into mechanical work to produce autonomous motion, and exhibit striking collective dynamics that biology relies on for essential functions. Controlling those dynamics and transport in synthetic systems has been particularly challenging. Here, we introduce the concept of spatially structured activity as a means of controlling and manipulating transport in active nematic liquid crystals consisting of actin filaments and light-sensitive myosin motors. Simulations and experiments are used to demonstrate that topological defects can be generated at will and then constrained to move along specified trajectories by inducing local stresses in an otherwise passive material. These results provide a foundation for the design of autonomous and reconfigurable microfluidic systems where transport is controlled by modulating activity with light.

Programming Solitons in Liquid Crystals Using Surface Chemistry.

AC electric fields cause three-dimensional orientational fluctuations (solitons) to form and rapidly propagate in confined films of liquid crystals (LCs), offering the basis of a new class of active soft matter (e.g., for accelerating mixing and transport processes in microscale chemical systems). How surface chemistry impacts the formation and trajectories of solitons, however, is not understood. Here, we show that self-assembled monolayers (SAMs) formed from alkanethiols on gold, which permit precise control over surface chemistry, are electrochemically stable over voltage and frequency windows (<100 V; 1 kHz) that lead to soliton formation in achiral nematic films of 4'-butyl-4-heptyl-bicyclohexyl-4-carbonitrile (CCN-47). By comparing soliton formation in LC films confined by SAMs formed from hexadecanethiol (C16SH) or pentadecanethiol (C15SH), we reveal that the electric field required for soliton formation increases with the LC anchoring energy: surfaces patterned with regions of C16SH and C15SH SAMs thus permit spatially controlled creation and annihilation of solitons necessary to generate a net flux of solitons. We also show that solitons propagate in orthogonal directions when confined by obliquely deposited gold films decorated with SAMs formed from C16SH or C15SH and that the azimuthal direction of propagation of solitons within achiral LC films possessing surface-induced twists is not unique but reflects variation in the spatial location of the solitons across the thickness of the twisted LC film. Finally, discontinuous changes in LC orientation induced by patterned surface anchoring lead to a range of new soliton behaviors including refraction, reflection, and splitting of solitons at the domain boundaries. Overall, our results provide new approaches for the controlled generation and programming of solitons with complex and precise trajectories, principles that inform new designs of chemical soft matter.

Director Distortion and Phase Modulation in Deformable Nematic and Smectic Liquid Crystal Spheroids.

The growing interest in integrating liquid crystals (LCs) into flexible and miniaturized technologies brings about the need to understand the interplay between spatially curved geometry, surface anchoring, and the order associated with these materials. Here, we integrate experimental methods and computational simulations to explore the competition between surface-induced orientation and the effects of deformable curved boundaries in uniaxially and biaxially stretched nematic and smectic microdroplets. We find that the director field of the nematic LCs upon uniaxial strain reorients and forms a larger twisted defect ring to adjust to the new deformed geometry of the stretched droplet. Upon biaxial extension, the director field initially twists in the now oblate geometry and subsequently transitions into a uniform vertical orientation at high strains. In smectic microdroplets, on the other hand, LC alignment transforms from a radial smectic layering to a quasi-flat layering in a compromise between interfacial and dilatation forces. Upon removing the mechanical strain, the smectic LC recovers its initial radial configuration; however, the oblate geometry traps the nematic LC in the metastable vertical state. These findings offer a basis for the rational design of LC-based flexible devices, including wearable sensors, flexible displays, and smart windows.

OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations.

We present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models while adding GPU acceleration and the ease of forcefield modification provided by OpenMM's Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of OpenMM's Custom Forces framework by devising and implementing two new potentials that allow us to address important aspects of protein folding and structure prediction and by testing the ability of the combined OpenAWSEM and Open3SPN2 to model protein-DNA binding. The first potential is used to describe the changes in effective interactions that occur as a protein becomes partially buried in a membrane. We also introduced an interaction to describe proteins with multiple disulfide bonds. Using simple pairwise disulfide bonding terms results in unphysical clustering of cysteine residues, posing a problem when simulating the folding of proteins with many cysteines. We now can computationally reproduce Anfinsen's early Nobel prize winning experiments by using OpenMM's Custom Forces framework to introduce a multi-body disulfide bonding term that prevents unphysical clustering. Our protein-DNA simulations show that the binding landscape is funneled towards structures that are quite similar to those found using experiments. In summary, this paper provides a simulation tool for the molecular biophysics community that is both easy to use and sufficiently efficient to simulate large proteins and large protein-DNA systems that are central to many cellular processes. These codes should facilitate the interplay between molecular simulations and cellular studies, which have been hampered by the large mismatch between the time and length scales accessible to molecular simulations and those relevant to cell biology.