Tian Tang

Design of biomimetic fibrillar interfaces: 2. Mechanics of enhanced adhesion.

This study addresses the strength and toughness of generic fibrillar structures. We show that the stress σc required to pull a fibril out of adhesive contact with a substrate has the form σc=σ0Φ(χ). In this equation, σ0 is the interfacial strength, Φ(χ) is a dimensionless function satisfying 0=Φ(χ)=1 and χ is a dimensionless parameter that depends on the interfacial properties, as well as the fibril stiffness and radius. Pull-off is flaw sensitive for χ≫1, but is flaw insensitive for χ<1. The important parameter χ also controls the stability of a homogeneously deformed non-fibrillar (flat) interface. Using these results, we show that the work to fail a unit area of fibrillar surface can be much higher than the intrinsic work of adhesion for a flat interface of the same material. In addition, we show that cross-sectional fibril dimensions control the pull-off force, which increases with decreasing fibril radius. Finally, an increase in fibril length is shown to increase the work necessary to separate a fibrillar interface. Besides our calculations involving a single fibril, we study the concept of equal load sharing (ELS) for a perfect interface containing many fibrils. We obtain the practical work of adhesion for an idealized fibrillated interface under equal load sharing. We then analyse the peeling of a fibrillar surface from a rigid substrate and establish a criterion for ELS.

Can a fibrillar interface be stronger and tougher than a non-fibrillar one?

Elasticity analysis and finite element simulations are carried out to study the strength of an elastic fibrillar interface. The fibrils are assumed to be in perfect contact with a rigid substrate. The adhesive interaction between the fibrils and the substrate is modelled by the Dugdale–Barenblatt model (DB). The condition for a fibrillar interface to be stronger than a non-fibrillar one is obtained for two regimes: (i) small fibril or flaw insensitive regime; (ii) large fibril or flaw sensitive regime. The transition between the two regimes is characterized by a dimensionless parameter that incorporates the material constants of the elastic fibrils and interfacial properties. The condition for a fibrillar interface to be tougher is also given. Lateral collapse is found to be detrimental to the strength and toughness of a fibrillar interface.

Molecular Dynamics Simulations of DNA/PEI Complexes: Effect of PEI Branching and Protonation State

Complexes formed by DNA and polyethylenimine (PEI) are of great research interest because of their application in gene therapy. In this work, we carried out all-atom molecular dynamics simulations to study eight types of DNA/PEI complexes, each of which was formed by one DNA duplex d(CGCGAATTCGCG)(2) and one PEI. We used eight different PEIs with four different degrees of branching and two protonation ratios of amine groups (23% and 46%) in the simulations to investigate how the branching degree and protonation state can affect the binding. We found that 46% protonated PEIs form more stable complexes with DNA, and the binding is achieved mainly through direct interaction between the protonated amine groups on PEI and the electronegative oxygens on the DNA backbone, with some degree of interaction with electronegative groove nitrogens/oxygens. For the 23% protonated PEIs, indirect interaction mediated by one or more water molecules plays an important role in binding. Compared with the protonation state, the degree of branching has a smaller effect on binding, which essentially diminishes at the protonation ratio of 46%. These simulations shed light on the detailed mechanism(s) of PEI binding to DNA, and may facilitate the design of PEI-based gene delivery carriers.

Collapse of single-walled carbon nanotubes

Single-walled carbon nanotubes with a circular cross section can collapse into ribbons under the influence of self-van der Waals interactions. We present closed-form results for the energetics of this self-collapse using continuum analysis verified by molecular simulations. Two critical tube radii are predicted by the continuum analysis: Rmin, below which there is no collapse; and Rmax, above which the collapsed configuration is energetically favored. We present simple and accurate analytical results for Rmin and Rmax as functions of two length scales, d0 and D∕Wflat, where d0 is the equilibrium distance between two flat parallel graphite sheets, Wflat is the work per unit area needed to separate the two sheets, and D is the effective bending stiffness of the tube.

Adhesion between single-walled carbon nanotubes

Continuum analysis and molecular simulations are carried out to study the adhesion between two identical single-walled carbon nanotubes. A critical radius Rmin=D∕Wflat is found below which the contact area is zero, where D is the effective bending stiffness of the nanotube, and Wflat is the work needed to separate two flat parallel graphite sheets of unit area in equilibrium. Using our theory, the change in the potential energy during the deformation is obtained and the theoretical result compares well with molecular simulations.

Modeling liquid bridge between surfaces with contact angle hysteresis.

This paper presents the behaviors of a liquid bridge when being compressed and stretched in a quasi-static fashion between two solid surfaces that have contact angle hysteresis (CAH). A theoretical model is developed to obtain the profiles of the liquid bridge given a specific separation between the surfaces. Different from previous models, both contact lines in the upper and lower surfaces were allowed to move when the contact angles reach their advancing or receding values. When the contact angles are between their advancing and receding values, the contact lines are pinned while the contact angles adjust to accommodate the changes in separation. Effects of CAH on both asymmetric and symmetric liquid bridges were analyzed. The model was shown to be able to correctly predict the behavior of the liquid bridge during a quasi-static compression/stretching loading cycle in experiments. Because of CAH, the liquid bridge can have two different profiles at the same separation during one loading and unloading cycle, and more profiles can be obtained during multiple cycles. The maximum adhesion force generated by the liquid bridge is found to be influenced by the CAH of surfaces. CAH also leads to energy cost during a loading cycle of the liquid bridge. In addition, the minimum separation between the two solid surfaces is shown to affect how the contact radii and angles change on the two surfaces as the liquid bridge is stretched.

A molecular dynamics simulation study on the effect of lipid substitution on polyethylenimine mediated siRNA complexation

Polycations have been explored as non-viral carriers for effective delivery of small interfering RNA (siRNA). Modifying polycations such as polyethylenimine (PEI) with lipid substitution was found to improve the siRNA delivery efficiency of polycationic carriers. However, the role of such lipid modification is not clear and remains to be probed at the atomistic level. In this work, we elucidate the role of lipid modification through a series of all-atom molecular dynamics simulations on siRNA complexation mediated by a native PEI and four analogous obtained by different lipid modifications. The lipid modification does not affect PEIs capability of neutralizing the siRNA charge, neither does it affect the polyion bridging which plays an important role in siRNA complexation. Significant linkages among the lipid modified PEIs via association of lipid side-groups are observed and this results in more stable and compact PEI/siRNA polyplexes. The lipid associations between short lipids form and break frequently while the lipid associations between long lipids are more stable. For PEIs modified with short lipids, increasing the lipid substitution level results in more compact and stable siRNA structure. For PEIs modified with long lipids, increasing the lipid substitution does not change the amount of PEI linkage via lipid association, and has a reverse effect on compacting siRNA structure due to increased steric hindrance brought by the lipid association on individual PEIs. The simulation results generally correlate well with experimental data and suggest a framework of designing and systematic evaluation of polycation-based siRNA carriers using molecular dynamics simulations.

Molecular Dynamics Simulations for Complexation of DNA with 2 kDa PEI Reveal Profound Effect of PEI Architecture on Complexation

A series of all-atom molecular dynamics (MD) simulations of the complexation between DNA and 2 kDa branched and linear polyethylenimines (PEIs) are reported in this study. The simulations revealed distinct binding modes of branched and linear PEIs to DNA, with branched PEIs adhering to the DNA surface like beads and linear PEIs adhering to the DNA surface like cords. The dynamics of each PEIs binding state to the DNA during the simulations and how the PEIs neutralize the DNA were quantified. For both branched and linear PEIs, the addition of salt ions similar to physiological conditions were found to have only a small effect on DNA/PEI complexation compared to salt-free conditions. The simulation results reported here will be helpful to understand the mechanism of action for the PEI-based gene carriers.

Molecular modeling of polynucleotide complexes.

Delivery of polynucleotides into patient cells is a promising strategy for treatment of genetic disorders. Gene therapy aims to either synthesize desired proteins (DNA delivery) or suppress expression of endogenous genes (siRNA delivery). Carriers constitute an important part of gene therapeutics due to limitations arising from the pharmacokinetics of polynucleotides. Non-viral carriers such as polymers and lipids protect polynucleotides from intra and extracellular threats and facilitate formation of cell-permeable nanoparticles through shielding and/or bridging multiple polynucleotide molecules. Formation of nanoparticulate systems with optimal features, their cellular uptake and intracellular trafficking are crucial steps for an effective gene therapy. Despite the great amount of experimental work pursued, critical features of the nanoparticles as well as their processing mechanisms are still under debate due to the lack of instrumentation at atomic resolution. Molecular modeling based computational approaches can shed light onto the atomic level details of gene delivery systems, thus provide valuable input that cannot be readily obtained with experimental techniques. Here, we review the molecular modeling research pursued on critical gene therapy steps, highlight the knowledge gaps in the field and providing future perspectives. Existing modeling studies revealed several important aspects of gene delivery, such as nanoparticle formation dynamics with various carriers, effect of carrier properties on complexation, carrier conformations in endosomal stages, and release of polynucleotides from carriers. Rate-limiting steps related to cellular events (i.e. internalization, endosomal escape, and nuclear uptake) are now beginning to be addressed by computational approaches. Limitations arising from current computational power and accuracy of modeling have been hindering the development of more realistic models. With the help of rapidly-growing computational power, the critical aspects of gene therapy are expected to be better investigated and direct comparison between more realistic molecular modeling and experiments may open the path for design of next generation gene therapeutics.

Design of bio-inspired fibrillar interfaces for contact and adhesion — theory and experiments

Geckos can adhere upside down on a horizontal surface and yet can climb rapidly on most vertical walls. This feat is accomplished using a hierarchical fibrillar interface. This paper reviews design principles of synthetic fibrillar interfaces that mimic surface structures in lizards and insects designed for enhanced contact and adhesion. In addition, we will address the role that statistics plays in quantifying fibrillar adhesion.