Pengyu Chen

Receptor-Mediated Endocytosis of Two-Dimensional Nanomaterials Undergoes Flat Vesiculation and Occurs by Revolution and Self-Rotation.

Two-dimensional nanomaterials, such as graphene and transitional metal dichalcogenide nanosheets, are promising materials for the development of antimicrobial surfaces and the nanocarriers for intracellular therapy. Understanding cell interaction with these emerging materials is an urgently important issue to promoting their wide applications. Experimental studies suggest that two-dimensional nanomaterials enter cells mainly through receptor-mediated endocytosis. However, the detailed molecular mechanisms and kinetic pathways of such processes remain unknown. Here, we combine computer simulations and theoretical derivation of the energy within the system to show that the receptor-mediated transport of two-dimensional nanomaterials, such as graphene nanosheet across model lipid membrane, experiences a flat vesiculation event governed by the receptor density and membrane tension. The graphene nanosheet is found to undergo revolution relative to the membrane and, particularly, unique self-rotation around its normal during membrane wrapping. We derive explicit expressions for the formation of the flat vesiculation, which reveals that the flat vesiculation event can be fundamentally dominated by a dimensionless parameter and a defined relationship determined by complicated energy contributions. The mechanism offers an essential understanding on the cellular internalization and cytotoxicity of the emerging two-dimensional nanomaterials.

Ligand–Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

Diffusion and Directionality of Charged Nanoparticles on Lipid Bilayer Membrane

Diffusion dynamics of charged nanoparticles on the lipid membrane is of essential importance to cellular functioning. Yet a fundamental insight into electrostatics-mediated diffusion dynamics of charged nanoparticles on the membrane is lacking and remains to be an urgent issue. Here we present the computational investigation to uncover the pivotal role of electrostatics in the diffusion dynamics of charged nanoparticles on the lipid membrane. Our results demonstrate diffusive behaviors and directional transport of a charged nanoparticle, significantly depending on the sign and spatial distribution of charges on its surface. In contrast to the Fickian diffusion of neutral nanoparticles, randomly charged nanoparticles undergo superdiffusive transport with directionality. However, the dynamics of uniformly charged nanoparticles favors Fickian diffusion that is significantly enhanced. Such observations can be explained in term of electrostatics-induced surface reconstruction and fluctuation of lipid membrane. We finally present an analytical model connecting surface reconstruction and local deformation of the membrane. Our findings bear wide implications for the understanding and control of the transport of charged nanoparticles on the cell membrane.

Shearing Janus Nanoparticles Confined in Two-Dimensional Space: Reshaped Cluster Configurations and Defined Assembling Kinetics.

The self-assembly of anisotropic nanoparticles (ANPs) possesses a wide array of potential applications in various fields, ranging from nanotechnology to material science. Despite intense research of the thermodynamic self-assembly of ANPs, elucidating their nonequilibrium behaviors under confinement still remains an urgent issue. Here, by performing simulation and theoretical justification, we present for the first time a study of the shear-induced behaviors of Janus spheres (the most elementary ANPs) confined in two-dimensional space. Our results demonstrate that the collective effects of shear and bonding structures can give rise to reshaped cluster configurations, featured by the chiral transition of clusters. Scaling analysis and numerical modeling are performed to quantitatively capture the assembling kinetics of dispersed Janus spheres, thereby suggesting an exotic way to bridge the gap between anisotropic and isotropic particles. The findings highlight confinement and shearing engineering as a versatile strategy to tailor the superstructures formed by ANPs toward unique properties.

Optimal Reactivity and Improved Self-Healing Capability of Structurally Dynamic Polymers Grafted on Janus Nanoparticles Governed by Chain Stiffness and Spatial Organization

Structurally dynamic polymers are recognized as a key potential to revolutionize technologies ranging from design of self-healing materials to numerous biomedical applications. Despite intense research in this area, optimizing reactivity and thereby improving self-healing ability at the most fundamental level pose urgent issue for wider applications of such emerging materials. Here, the authors report the first mechanistic investigation of the fundamental principle for the dependence of reactivity and self-healing capabilities on the properties inherent to dynamic polymers by combining large-scale computer simulation, theoretical analysis, and experimental discussion. The results allow to reveal how chain stiffness and spatial organization regulate reactivity of dynamic polymers grafted on Janus nanoparticles and mechanically mediated reaction in their reverse chemistry, and, particularly, identify that semiflexible dynamic polymers possess the optimal reactivity and self-healing ability. The authors also develop an analytical model of blob theory of polymer chains to complement the simulation results and reveal essential scaling laws for optimal reactivity. The findings offer new insights into the physical mechanism in various systems involving reverse/dynamic chemistry. These studies highlight molecular engineering of polymer architecture and intrinsic property as a versatile strategy in control over the structural responses and functionalities of emerging materials with optimized self-healing capabilities.

Physical principles of graphene cellular interactions: computational and theoretical accounts

As a class of two-dimensional (2D) nanomaterials, graphene and its derivatives have aroused tremendous interest in materials chemistry research ranging from synthesis, property characterization to technological application. In particular, the use of these nanomaterials in biomedicine has been steadily growing, which at the same time ignites great concern on their potential cytotoxicity and impacts on health and the environment. A thorough understanding and thereby controlling of the cellular interactions of graphene-based nanomaterials (GBNs) is critical for the development of guidelines for safer biomedical applications and for the management of graphene related health and environmental issues. This review article highlights the most recent advances in investigating physiochemical mechanisms of cellular interactions of GBNs, focusing on the approaches of tailored computer simulations and theoretical analysis. We review how the energies and forces govern the states and kinetic pathways of these interactions and depend on the physical and chemical characteristics of GBNs as well as the components and biomechanical properties of the cell membrane. In addition, we discuss the relation of the simulation and theoretical results to some important experimental findings towards the mechanisms of cytotoxicity and antibacterial activity of GBNs. This review concludes with a discussion on the challenges facing the field, and future directions from the perspective of computational and theoretical methodologies.

How Implementation of Entropy in Driving Structural Ordering of Nanoparticles Relates to Assembly Kinetics: Insight through 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. In particular, such systems comprise binary Janus nanoparticles at the fluid-fluid interface and undergo phase transition driven by entropy and controlled by the polymerization reaction initiated from the surfaces of just one component of nanoparticles. Our simulations demonstrate that the competition between the reaction rate and the diffusive dynamics of nanoparticles governs the implementation of entropy in driving the phase transition from randomly mixed phase to intercalated phase in these interfacial nanoparticle mixtures, which thereby results in diverse kinetic pathways. At low reaction rates, the transition exhibits abrupt jump in the mixing parameter, in a similar way to first-order, equilibrium phase transition. Increasing the reaction rate diminishes the jumps until the transitions become continuous, behaving as a second-order-like phase transition, where a critical exponent, characterizing the transition, can be identified. We finally develop an analytical model of the blob theory of polymer chains to complement the simulation results and reveal essential scaling laws of the entropy-driven phase behaviors. In effect, our results allow for further opportunities to amplify the entropic contributions to the materials design via kinetic control.

Bacteria-Activated Janus Particles Driven by Chemotaxis

In the development of biocompatible nano-/micromotors for drug and cargo delivery, motile bacteria represent an excellent energy source for biomedical applications. Despite intense research of the fabrication of bacteria-based motors, how to effectively utilize the instinctive responses of bacteria to environmental stimuli in the fabrication process, particularly, chemotaxis, remains an urgent and critical issue. Here, by developing a molecular-dynamics model of bacterial chemotaxis, we present an investigation of the transport of a bacteria-activated Janus particle driven by chemotaxis. Upon increasing the stimuli intensity, we find that the transport of the Janus particle undergoes an intriguing second-order state transition: from a composite random walk, combining power-law-distributed truncated Lévy flights with Brownian jiggling, to an enhanced directional transport with size-dependent reversal of locomotion. A state diagram of Janus-particle transport depending on the stimuli intensity and particle size is presented, which allows approaches to realize controllable and predictable propulsion directions. The physical mechanism of these transport behaviors is revealed by performing a theoretical modeling based on the bacterial noise and Janus geometries. Our findings could provide a fundamental insight into the physics underlying the transport of anisotropic particles driven by microorganisms and highlight stimulus-response techniques and asymmetrical design as a versatile strategy to possess a wide array of potential applications for future biocompatible nano-/microdevices.