Self-Assembly at Curved Biointerfaces.

Most of the biological interfaces are curved. Understanding the organizational structures and interaction patterns at such curved biointerfaces is therefore crucial not only for deepening our comprehension of the principles that govern life processes but also for designing and developing targeted drugs aimed at diseased cells and tissues. Despite the considerable efforts dedicated to this area of research, our understanding of curved biological interfaces is still limited.

Nonequilibrium Dynamic Phase Diagram for Transmembrane Transport of Active Particles.

In recent years, there has been considerable push toward the biomedical applications with active particles, which have great potential to revolutionize disease diagnostics and therapy. The direct penetration of active particles through the cell membrane leads to more efficient intracellular delivery than previously considered endocytosis processes but may cause membrane disruption. Understanding fundamental behaviors of cell membranes in response to such extreme impacts by active particles is crucial to develop active particle-based biomedical technologies and manage health and safety issues in this emerging field.

Unconventionally fast transport through sliding dynamics of rodlike particles in macromolecular networks.

Transport of rodlike particles in confinement environments of macromolecular networks plays crucial roles in many important biological processes and technological applications. The relevant understanding has been limited to thin rods with diameter much smaller than network mesh size, although the opposite case, of which the dynamical behaviors and underlying physical mechanisms remain unclear, is ubiquitous. Here, we solve this issue by combining experiments, simulations and theory.

Hydrodynamic Anisotropy of Depletion in Nonequilibrium.

Active colloids in a bath of inert particles of smaller size cause anisotropic depletion. The active hydrodynamics of this nonequilibrium phenomenon, which is fundamentally different from its equilibrium counterpart and passive particles in an active bath, remains scarcely understood. Here we combine mesoscale hydrodynamic simulation as well as theoretical analysis to examine the physical origin for the active depletion around a self-propelled noninteractive colloid.

The entropy-controlled strategy in self-assembling systems.

Self-assembly of various building blocks has been considered as a powerful approach to generate novel materials with tailorable structures and optimal properties. Understanding physicochemical interactions and mechanisms related to structural formation and transitions is of essential importance for this approach. Although it is well-known that diverse forces and energies can significantly contribute to the structures and properties of self-assembling systems, the potential entropic contribution remains less well understood.

Configurational Entropy-Enabled Thermostability of Cell Membranes in Extremophiles: From Molecular Mechanism to Bioinspired Design.

Understanding physicochemical interactions and mechanisms related to the cell membranes of lives under extreme conditions is of essential importance but remains scarcely explored. Here, using a combination of computer simulations and experiments, we demonstrate that the structural integrity and controllable permeability of cell membranes at high temperatures are predominantly directed by configurational entropy emerging from distorted intermolecular organization of bipolar tethered lipids peculiar to the extremophiles. Detailed simulations across multiple scales─from an all-atom exploration of molecular mechanism to a mesoscale examination of its universal nature─suggest that this configurational entropy effect can be generalized to diverse systems, such as block copolymers.

Studies on the Synergistic Effect of Tandem Semi-Stable Complementary Domains on Sequence-Defined DNA Block Copolymers.

Tandem semi-stable complementary domains play an important role in life, while the role of these domains in the folding process of nucleic acid molecules has not been systematically studied. Here, we designed a clean model system by synthesizing sequence-defined DNA-OEG copolymers composed of ssDNA fragments with palindromic sequences and orthogonal oligo(tetraethylene glycol) (OEG) linkers. By altering the lengths of DNA units (6-12 nt) and OEG linkers (Xn = 0-4) separately, we systematically studied how stabilities of tandem complementary domains and connecting flexibilities affect the assembly topology.

"Shutter" Effects Enhance Protein Diffusion in Dynamic and Rigid Molecular Networks.

Hydrogels have been widely applied to understand the fundamental functions and mechanism of a natural extracellular matrix (ECM). However, revealing the high permeability of ECM through synthetic hydrogels is still challenged by constructing analogue networks with rigid and dynamic properties. Here, in this study, taking advantage of the rigidity and dynamic binding of DNA building blocks, we have designed a model hydrogel system with structural similarity to ECM, leading to enhanced diffusion for proteins compared with a synthetic polyacrylamide (PAAm) hydrogel.

Understanding Interfacial Nanoparticle Organization through Simulation and Theory: A Review.

Understanding the behaviors of nanoparticles at interfaces is crucial not only for the design of novel nanostructured materials with superior properties but also for a better understanding of many biological systems where nanoscale objects such as drug molecules, viruses, and proteins can interact with various interfaces. Theoretical studies and tailored computer simulations offer unique approaches to investigating the evolution and formation of structures as well as to determining structure-property relationships regarding the interfacial nanostructures. In this feature article, we summarize our efforts to exploit computational approaches as well as theoretical modeling in understanding the organization of nanoscale objects at the interfaces of various systems.

Synthesis and biological evaluation of 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine covalent inhibitors as potential agents for the treatment of acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) mutation has been strongly associated with increased risk of relapse, and the irreversible covalent FLT3 inhibitors had the potential to overcome the drug-resistance. In this study, a series of simplified 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives containing two types of Michael acceptors (vinyl sulfonamide, acrylamide) were conveniently synthesized to target FLT3 and its internal tandem duplications (ITD) mutants irreversibly. The kinase inhibitory activities showed that compound C14 displayed potent inhibition activities against FLT3 (IC = 256 nM) and FLT3-ITD by 73 % and 25.

Topology mediates transport of nanoparticles in macromolecular networks.

Diffusion transport of nanoparticles in confined environments of macromolecular networks is common in diverse physical systems and regulates many biological responses. Macromolecular networks possess various topologies, featured by different numbers of degrees and genera. Although the network topologies can be manipulated from a molecular level, how the topology impacts the transport of nanoparticles in macromolecular networks remains unexplored.

Multi-scale computer-aided design and photo-controlled macromolecular synthesis boosting uranium harvesting from seawater.

By integrating multi-scale computational simulation with photo-regulated macromolecular synthesis, this study presents a new paradigm for smart design while customizing polymeric adsorbents for uranium harvesting from seawater. A dissipative particle dynamics (DPD) approach, combined with a molecular dynamics (MD) study, is performed to simulate the conformational dynamics and adsorption process of a model uranium grabber, i.e.

Superstretchable, yet stiff, fatigue-resistant ligament-like elastomers.

Ligaments are flexible and stiff tissues around joints to support body movements, showing superior toughness and fatigue-resistance. Such a combination of mechanical properties is rarely seen in synthetic elastomers because stretchability, stiffness, toughness, and fatigue resistance are seemingly incompatible in materials design. Here we resolve this long-standing mismatch through a hierarchical crosslinking design.

[Quality value transmitting of substance benchmarks of Zhuru Decoction].

A total of 18 batches of Zhuru Decoction samples were prepared. Chromatographic fingerprints were established for Zhuru Decoction and single decoction pieces, the content of which was then determined. The extraction rate ranges, content, and transfer rate ranges of puerarin, liquiritin, and glycyrrhizic acid, together with the common peaks and the similarity range of the fingerprints, were determined to clarify key quality attributes of Zhuru Decoction.

Design of Entropy-Driven Polymers Resistant to Bacterial Attachment via Multicomponent Reactions.

Nonbactericidal polymers that prevent bacterial attachment are important for public health, environmental protection, and avoiding the generation of superbugs. Here, inspired by the physical bactericidal process of carbon nanotubes and graphene derivatives, we develop nonbactericidal polymers resistant to bacterial attachment by using multicomponent reactions (MCRs) to introduce molecular "needles" (rigid aliphatic chains) and molecular "razors" (multicomponent structures) into polymer side chains. Computer simulation reveals the occurrence of spontaneous entropy-driven interactions between the bacterial bilayers and the "needles" and "razors" in polymer structures and provides guidance for the optimization of this type of polymers for enhanced resistibility to bacterial attachment.

Entropy-Driven Unconventional Crystallization of Spherical Colloidal Nanocrystals Confined in Wide Cylinders.

The densest packings of identical spherical colloidal nanocrystals in a thin cylinder generally give rise to confinement-induced chiral ordering. Here, we demonstrate that entropy can invalidate Pauling's packing rules for the nanocrystals confined in wide cylinders and novel ordered phases, where chiral ordering is broken, emerge. The nucleation and growth of spherical colloidal nanocrystals in the wide cylinders exhibit unique mechanisms which are distinctly different from that of thin ones.

Cellular Uptake of Active Particles.

Active particles are widely recognized to potentially revolutionize technologies in numerous biomedical applications. However, the physical origin behind cellular uptake of these particles in the nonequilibrium state remains scarcely understood. Here we combine Brownian dynamics simulation as well as theoretical analysis to provide the criterion for cellular uptake of active particles, related to various physical attributes.

Entropy-Mediated Mechanomutable Microstructures and Mechanoresponsive Thermal Transport of Nanoparticle Self-Assembly in Block Copolymers.

Despite decades of intense research efforts on the self-assembly of nanoparticles in mesophase-forming copolymers, the progress in practical applications is impeded by the lack of knowledge about the dynamic transition of such hierarchical nanostructures in an environment bearing an external load. Here, we show that the hierarchical self-assembly of nanoparticles in block copolymer scaffolds can be made to significantly alternate by external compression, characterized by a continuous and reverse transition among various distribution states of nanoparticles in their preferential domains. Theoretical analysis reveals that compression-induced transition of the nanoparticle distribution can be fundamentally attributed to unique entropic effects originating from the compacted block chains.

Optimal ligand-receptor binding for highly efficient capture of vesicles in nanofluidic transportation.

Optimizing ligand-receptor binding is essential for exploiting advanced biomedical applications from targeting drug delivery to biosensing. A key challenge is how optimized ligand-receptor binding can be realized during the transport of ligand-modified soft materials through a nanofluidic channel. Here, by combining computer simulations and theoretical analysis, we report that the ligand-receptor binding and resulting capture probability of ligand-functionalized vesicles nonmonotonically depend on their some intrinsic properties, e.

Entropic Effects in Polymer Nanocomposites.

Polymer nanocomposite materials, consisting of a polymer matrix embedded with nanoscale fillers or additives that reinforce the inherent properties of the matrix polymer, play a key role in many industrial applications. Understanding of the relation between thermodynamic interactions and macroscopic morphologies of the composites allow for the optimization of design and mechanical processing. This review article summarizes the recent advancement in various aspects of entropic effects in polymer nanocomposites, and highlights molecular methods used to perform numerical simulations, morphologies and phase behaviors of polymer matrices and fillers, and characteristic parameters that significantly correlate with entropic interactions in polymer nanocomposites.

Hierarchical Crystals Formed from DNA-Functionalized Janus Nanoparticles.

Harnessing anisotropic interactions in a DNA-mediated nanoparticle assembly holds great promise as a rational strategy to advance this important area. Here, using molecular dynamics simulations, we report the formation of novel hierarchical crystalline assemblies of Janus nanoparticles functionalized with two types of DNA chains (DNA-JNPs). We find that in addition to the primary nanoparticle crystallization into face-centered cubic (FCC) structure, sequence-specific DNA hybridization events further direct the rotational orientation of the DNA-JNPs to diverse secondary crystalline phases including simple cubic (SC), tetragonally ordered cylinder (P4), and lamella (L) structures, which are mapped in the phase diagrams relating to various asymmetric parameters.

How Implementation of Entropy in Driving Structural Ordering of Nanoparticles Relates to Assembly Kinetics: Insight into Reaction-Induced Interfacial Assembly of Janus Nanoparticles.

The ability to understand and exploit entropic contributions to ordering transition is of essential importance in the design of self-assembling systems with well-controlled structures. However, much less is known about the role of assembly kinetics in entropy-driven phase behaviors. Here, by combining computer simulations and theoretical analysis, we report that the implementation of entropy in driving phase transition significantly depends on the kinetic process in the reaction-induced self-assembly of newly designed nanoparticle systems.