Influence of magnetic convection on separation efficiency in magnetophoretic microfluidic processes: a combined simulation and experimental study.

This work explores the complex hydrodynamics in magnetophoretic microfluidic processes, focusing on the interplay of forces and particle concentrations. The study employs a combined simulation and experimental approach to investigate the impact of magnetophoresis on magneto-responsive nanoparticles (MNPs) and their environment, including non-magneto-responsive nanoparticles (non-MNPs) in a microfluidic system. Our findings reveal that the motion of MNPs induces a hydrodynamic convective motion of non-MNPs, significantly affecting the separation efficiency and purity of the particles.

Sequence-Sensitivity in Functional Synthetic Polymer Properties.

Recently, a new class of synthetic methyl methacrylate-based random heteropolymers (MMA-based RHPs) has displayed protein-like properties. Their function appears to be insensitive to the precise sequence. Here, through atomistic molecular dynamics simulation, we show that there are universal protein-like features of MMA-based RHPs that are insensitive to the sequence, and mostly depend on the overall composition.

A Computationally Informed Unified View on the Effect of Polarity and Sterics on the Glass Transition in Vinyl-based Polymer Melts.

We unveil a unified view on the effect of side chains on the glass transition temperatures () in polymer melts by using molecular dynamics simulations, density functional theory calculations, and available experimental data. We use acrylates as a model system and evaluate the effect of -alkyl side chains on . We find that backbone dihedral angle fluctuations follow established patterns due to sterics, as expected.

Dynamic transformation of bio-inspired single-chain nanoparticles at interfaces.

The interfacial behavior of macromolecules dictates their intermolecular interactions, which can impact the processing and application of polymers for pharmaceutical and synthetic use. Using molecular dynamics simulations, we observe the evolution of a random heteropolymer in the presence of liquid-liquid interfaces. The system of interest forms single-chain nanoparticles through hydrophobic collapse in water, lacking permanent crosslinks and making their morphology mutable in new environments.

The interplay between adsorption and aggregation of von Willebrand factor chains in shear flows.

Von Willebrand factor (VWF) is a giant extracellular glycoprotein that carries out a key adhesive function during primary hemostasis. Upon vascular injury and triggered by the shear of flowing blood, VWF establishes specific interactions with several molecular partners in order to anchor platelets to collagen on the exposed subendothelial surface. VWF also interacts with itself to form aggregates that, adsorbed on the surface, provide more anchor sites for the platelets.

Population-based heteropolymer design to mimic protein mixtures.

Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively.

Mechano-Chemical Effect of Gelatin- and HA-Based Hydrogels on Human Retinal Progenitor Cells.

Engineering matrices for cell therapy requires design criteria that include the ability of these materials to support, protect and enhance cellular behavior in vivo. The chemical and mechanical formulation of the biomaterials can influence not only target cell phenotype but also cellular differentiation. In this study, we have demonstrated the effect of a gelatin (Gtn)-hyaluronic acid (HA) hydrogel on human retinal progenitor cells (hRPCs) and show that by altering the mechanical properties of the materials, cellular behavior is altered as well.

Emergence of layered nanoscale mesh networks through intrinsic molecular confinement self-assembly.

Block copolymer self-assembly is a powerful tool for two-dimensional nanofabrication; however, the extension of this self-assembly concept to complex three-dimensional network structures is limited. Here we report a simple method to experimentally generate three-dimensional layered mesh morphologies through intrinsic molecular confinement self-assembly. We designed triblock bottlebrush polymers with two Janus domains: one perpendicular and one parallel to the polymer backbone.

Experimental and Computational Evaluation of Self-Assembled Morphologies in Diblock Janus Bottlebrush Copolymers.

Diblock Janus-type "A--B" bottlebrush copolymers (di-JBBCPs) consist of a backbone with alternating A and B side chains, in contrast to the side chain arrangement of conventional bottlebrush copolymers. As a result, A and B blocks of di-JBBCPs can microphase-separate perpendicular to the backbone, which is located at the interface between the two blocks. A reparametrized dissipative particle dynamics (DPD) model is used to theoretically investigate the self-assembly of di-JBBCPs and to compare with the experimental results of a range of polystyrene--polydimethylsiloxane di-JBBCPs.

Molecular signatures of the glass transition in polymers.

The glass transition temperature (T_{g}) is one of the most fundamental properties of polymers. T_{g} is predicted by some theories as a sudden change in a "macroscopic" quantity (e.g.

Symmetry-Breaking and Self-Sorting in Block Copolymer-Based Multicomponent Nanocomposites.

Co-assembly of inorganic nanoparticles (NPs) and nanostructured polymer matrix represents an intricate interplay of enthalpic or entropic forces. Particle size largely affects the phase behavior of the nanocomposite. Theoretical studies indicate that new morphologies would emerge when the particles become comparable to the soft matrix's size, but this has rarely been supported experimentally.

STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity.

Activation of the innate immune STimulator of INterferon Genes (STING) pathway potentiates antitumour immunity, but systemic delivery of STING agonists to tumours is challenging. We conjugated STING-activating cyclic dinucleotides (CDNs) to PEGylated lipids (CDN-PEG-lipids; PEG, polyethylene glycol) via a cleavable linker and incorporated them into lipid nanodiscs (LNDs), which are discoid nanoparticles formed by self-assembly. Compared to state-of-the-art liposomes, intravenously administered LNDs carrying CDN-PEG-lipid (LND-CDNs) exhibited more efficient penetration of tumours, exposing the majority of tumour cells to STING agonist.

Coarse-Grained Simulations Suggest Potential Competing Roles of Phosphoinositides and Amphipathic Helix Structures in Membrane Curvature Sensing of the AP180 N-Terminal Homology Domain.

The generation and sensing of membrane curvature by proteins has become of increasing interest to researchers with multiple mechanisms, from hydrophobic insertion to protein crowding, being identified. However, the role of charged lipids in the membrane curvature-sensing process is still far from understood. Many proteins involved in endocytosis bind phosphatidylinositol 4,5-bisphosphate (PIP2) lipids, allowing these proteins to accumulate at regions of local curvature.

Solvent Remodeling in Single-Chain Amphiphilic Heteropolymer Systems.

This work demonstrates the remodeling of single-chain nanoparticles (SCNPs) upon a transition to organic solvent through molecular dynamics simulations. Methacrylate-based random heteropolymers (RHPs), assembled via transient noncovalent linkages in water, have shown promise in an assortment of applications that harness their bio-inspired properties. While their molecular behavior has been broadly characterized in aqueous environments, many newer applications include the use of organic solvent rather than bio-mimetic conditions.

A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy.

Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN.

Multivalent polymers can control phase boundary, dynamics, and organization of liquid-liquid phase separation.

Multivalent polymers are a key structural component of many biocondensates. When interacting with their cognate binding proteins, multivalent polymers such as RNA and modular proteins have been shown to influence the liquid-liquid phase separation (LLPS) boundary to both control condensate formation and to influence condensate dynamics after phase separation. Much is still unknown about the function and formation of these condensed droplets, but changes in their dynamics or phase separation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's Disease.

Metallic Nanomeshes Fabricated by Multimechanism Directed Self-Assembly.

The directed self-assembly of block copolymers (BCPs) is a powerful motif for the continued scaling of feature sizes for nanoscale devices. A multimechanism directed self-assembly (MMDSA) method is described that generates orthogonal meshes from a polystyrene--poly-2-vinylpyridine BCP that is subsequently metallized with Pt. The MMDSA process takes advantage of three different mechanisms, trench wall guidance, edge nucleation, and underlayer guidance, to align the mesh with respect to substrate features.

Diversifying Composition Leads to Hierarchical Composites with Design Flexibility and Structural Fidelity.

Although significant progress has been made in the self-assembly of nanostructures, present successes heavily rely on precision in building block design, composition, and pair interactions. These requirements fundamentally limit our ability to synthesize macroscopic materials where the likelihood of impurity inclusion escalates and, more importantly, to access molecular-to-nanoscopic-to-microscopic-to-macroscopic hierarchies, since the types and compositions of building blocks vary at each stage. Inspired by biological blends and high-entropy alloys, we hypothesize that diversifying the blend's composition can overcome these limitations.

Nanoparticle Assembly in High Polymer Concentration Solutions Increases Superlattice Stability.

Polymer nanocomposites are made by combining a nanoscale filler with a polymer matrix, where polymer-particle interactions can enhance matrix properties and introduce behaviors distinct from either component. Manipulating particle organization within a composite potentially allows for better control over polymer-particle interactions, and the formation of ordered arrays can introduce new, emergent properties not observed in random composites. However, self-assembly of ordered particle arrays typically requires weak interparticle interactions to prevent kinetic traps, making these assemblies incompatible with most conventional processing techniques.

Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix.

Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific motifs which bind to the membrane, connecting it to the internal cytoskeletal machinery.

Effect of Molecular Architecture on the Self-Assembly of Bottlebrush Copolymers.

The characteristics of a new architecture of bottlebrush copolymers (BBCPs) self-assembly were studied using self-consistent field theory. In this molecule, a series of AB linear diblock side chains were connected at the diblock junction using a C backbone. The control over the linker length and its chemical nature created an additional constraint on the intrinsic AB diblock microphase separation.

Controlling Growth Factor Diffusion by Modulating Water Content in Injectable Hydrogels.

Recent advancements in the delivery of therapeutics for retinal diseases include the development of injectable hydrogels, networks of one or more hydrophilic polymers that contain a high-volume fraction of water. These systems are of particular interest due to their biocompatibility, permeability to water-soluble metabolites, and function as minimally invasive injectable delivery vehicles. Recently, hydrogels for ophthalmic applications have been developed that display a controlled release of factors necessary for cellular survival and proliferation.

Machine Learning Predictions of Block Copolymer Self-Assembly.

Directed self-assembly of block copolymers is a key enabler for nanofabrication of devices with sub-10 nm feature sizes, allowing patterning far below the resolution limit of conventional photolithography. Among all the process steps involved in block copolymer self-assembly, solvent annealing plays a dominant role in determining the film morphology and pattern quality, yet the interplay of the multiple parameters during solvent annealing, including the initial thickness, swelling, time, and solvent ratio, makes it difficult to predict and control the resultant self-assembled pattern. Here, machine learning tools are applied to analyze the solvent annealing process and predict the effect of process parameters on morphology and defectivity.

Polymer Stiffness Regulates Multivalent Binding and Liquid-Liquid Phase Separation.

Multivalent binding is essential to many biological processes because it builds high-affinity bonds by using several weak binding interactions simultaneously. Multivalent polymers have shown promise as inhibitors of toxins and other pathogens, and they are important components in the formation of biocondensates. Explaining how structural features of these polymers change their binding and subsequent control of phase separation is critical to designing better pathogen inhibitors and also to understanding diseases associated with membraneless organelles.