Xinghua Shi

Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation

Materials with high aspect ratio, such as carbon nanotubes and asbestos fibres, have been shown to cause length-dependent toxicity in certain cells because these long materials prevent complete ingestion and this frustrates the cell. Biophysical models have been proposed to explain how spheres and elliptical nanostructures enter cells, but one-dimensional nanomaterials have not been examined. Here, we show experimentally and theoretically that cylindrical one-dimensional nanomaterials such as carbon nanotubes enter cells through the tip first. For nanotubes with end caps or carbon shells at their tips, uptake involves tip recognition through receptor binding, rotation that is driven by asymmetric elastic strain at the tube-bilayer interface, and near-vertical entry. The precise angle of entry is governed by the relative timescales for tube rotation and receptor diffusion. Nanotubes without caps or shells on their tips show a different mode of membrane interaction, posing an interesting question as to whether modifying the tips of tubes may help avoid frustrated uptake by cells.

The nature of strength enhancement and weakening by pentagon–heptagon defects in graphene

The two-dimensional crystalline structures in graphene challenge the applicability of existing theories that have been used for characterizing its three-dimensional counterparts. It is crucial to establish reliable structure-property relationships in the important two-dimensional crystals to fully use their remarkable properties. With the success in synthesizing large-area polycrystalline graphene, understanding how grain boundaries (GBs) in graphene alter its physical properties is of both scientific and technological importance. A recent work showed that more GB defects could counter intuitively give rise to higher strength in tilt GBs (ref. 10). We show here that GB strength can either increase or decrease with the tilt, and the behaviour can be explained well by continuum mechanics. It is not just the density of defects that affects the mechanical properties, but the detailed arrangements of defects are also important. The strengths of tilt GBs increase as the square of the tilt angles if pentagon-heptagon defects are evenly spaced, and the trend breaks down in other cases. We find that mechanical failure always starts from the bond shared by hexagon-heptagon rings. Our present work provides fundamental guidance towards understanding how defects interact in two-dimensional crystals, which is important for using high-strength and stretchable graphene for biological and electronic applications.

Tunable rigidity of (polymeric core)-(lipid shell) nanoparticles for regulated cellular uptake

Core-shell nanoparticles (NPs) with lipid shells and varying water content and rigidity but with the same chemical composition, size, and surface properties are assembled using a microfluidic platform. Rigidity can dramatically alter the cellular uptake efficiency, with more-rigid NPs able to pass more easily through cell membranes. The mechanism accounting for this rigidity-dependent cellular uptake is revealed through atomistic-level simulations.

Tunable Water Channels with Carbon Nanoscrolls

Molecular dynamics simulations and theoretical analyses are performed to show that the flow rate of water through the core of carbon nanoscrolls (CNSs) can be adjusted over a broad range through the effective surface energy, which in turn can be tuned by an applied DC or AC electric field. The results suggest that the CNSs hold great promise for applications such as tunable water and ion channels, nanofluidic devices, and nanofilters, as well as tunable gene- and drug-delivery systems.

A translational nanoactuator based on carbon nanoscrolls on substrates

Inspired by recent experimental studies on the fabrication of carbon nanoscrolls (CNSs) on solid substrates, we perform theoretical study and molecular dynamics simulations to investigate the translational rolling/unrolling of a CNS on rigid substrate. We show that a substrate-supported CNS can be controlled to roll forward and backward by tuning its interlayer interaction energy via an external field. The typical energy release rate per unit area of rolling for such controllable and reversible linear motion is estimated to be in the range of (−0.06)–0.08 nN/nm, indicating promising applications as actuators and motors in nanomechanical systems.

Microfluidic Synthesis of Hybrid Nanoparticles with Controlled Lipid Layers: Understanding Flexibility-Regulated Cell–Nanoparticle Interaction

The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell-particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell-particle interaction may have important implications for designing drug nanocarriers.

Microfluidic Synthesis of Rigid Nanovesicles for Hydrophilic Reagents Delivery

We present a hollow-structured rigid nanovesicle (RNV) fabricated by a multi-stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside, without complicated synthesis, extensive use of emulsifiers and stabilizers, and laborious purification procedures. The RNV contains a hollow water core, a rigid poly (lactic-co-glycolic acid) (PLGA) shell, and an outermost lipid layer. The formation mechanism of the RNV is investigated by dissipative particle dynamics (DPD) simulations. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside the hollow water core of RNV is ≈90 %. In comparison with the combination of free Dox and siRNA, RNV that co-encapsulate siRNA and doxorubicin (Dox) reveals a significantly enhanced anti-tumor effect for a multi-drug resistant tumor model.

A universal law for cell uptake of one-dimensional nanomaterials.

Understanding cell interaction with one-dimensional nanomaterials, including nanotubes, nanowires, nanofibers, filamentous bacteria, and certain nanoparticle chains, has fundamental importance to many applications such as biomedical diagnostics, therapeutics, and nanotoxicity. Here we show that cell uptake of one-dimensional nanomaterials via receptor-mediated endocytosis is dominated by a single dimensionless parameter that scales with the membrane tension and radius of the nanomaterial and inversely with the membrane bending stiffness. It is shown that as cell membrane internalizes one-dimensional nanomaterials the uptake follows a near-perpendicular entry mode at small membrane tension but it switches to a near-parallel interaction mode at large membrane tension.

Gigahertz breathing oscillators based on carbon nanoscrolls

Theoretical study and molecular dynamics simulations are performed to investigate the gigahertz “breathing” oscillatory motion of a carbon nanoscroll (CNS). It is shown that the oscillation frequency depends on surface energy, bending stiffness, interlayer spacing, and length of the basal graphene sheet of the CNS, and that energy dissipation in the system can be controlled by adjusting temperature, graphene length, and surface energy. The analysis indicates potential applications of CNS in nanomechanical devices such as nanooscillators, nanoactuators, as well as drug and gene delivery systems.

Cellular entry of graphene nanosheets: the role of thickness, oxidation and surface adsorption

Coarse grained molecular dynamics simulations are conducted to study the interaction of graphene nanosheets with a lipid bilayer, focusing on the effects of graphene thicknesses (single/multi-layered graphene), oxidation and surface absorption by lipid molecules. The results show that a hydrophobic corner of graphene can pierce into the bilayer, while different oxidations of the nanosheets affect their final equilibrium configurations in the bilayer: lying across or within the hydrophobic core of the bilayer. The underlying mechanism is clarified by calculating the energy barrier for graphene piercing into the bilayer. Our studies provide fundamental guidance towards understanding how graphene enters cells, which is important for biomedical diagnostics and therapies, and for managing health impacts following occupational or environmental exposure.