Bioconjugation of COL1 protein on liquid-like solid surfaces to study tumor invasion dynamics.

Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.

The effect of surface roughness and viscoelasticity on rubber adhesion.

Adhesion between silica glass or acrylic balls and silicone elastomers and various industrial rubbers is investigated. The work of adhesion during pull-off is found to strongly vary depending on the system, which we attribute to the two opposite effects: (1) viscoelastic energy dissipation close to an opening crack tip and (2) surface roughness. Introducing surface roughness on the glass ball is found to increase the work of adhesion for soft elastomers, while for the stiffer elastomers it results in a strong reduction in the work of adhesion. For the soft silicone elastomers a strong increase in the work of adhesion with increasing pull-off velocity is observed, which may result from the non-adiabatic processes associated with molecular chain pull-out. In general, the work of adhesion is decreased after repeated contacts due to the transfer of molecules from the elastomers to the glass ball. Thus, extracting the free chains (oligomers) from the silicone elastomers is shown to make the work of adhesion independent of the number of contacts. The viscoelastic properties (linear and nonlinear) of all of the rubber compounds are measured, and the velocity dependent crack opening propagation energy at the interface is calculated. Silicone elastomers show a good agreement between the measured work of adhesion and the predicted results, but carbon black filled hydrogenated nitrile butadiene rubber compounds reveal that strain softening at the crack tip may play an important role in determining the work of adhesion. Additionally, adhesion measurement under submerged conditions in distilled water and water + soap solutions are also performed: a strong reduction in the work of adhesion is measured for the silicone elastomers submerged in water, and a complete elimination of adhesion is found for the water + soap solution attributed to an osmotic repulsion between the negatively charged surface of the glass and the elastomer.

Elastic modulus and hydraulic permeability of MDCK monolayers.

The critical role of cell mechanics in tissue health has led to the development of many in vitro methods that measure the elasticity of the cytoskeleton and whole cells, yet the connection between these local cell properties and bulk measurements of tissue mechanics remains unclear. To help bridge this gap, we have developed a monolayer indentation technique for measuring multi-cellular mechanics in vitro. Here, we measure the elasticity of cell monolayers and uncover the role of fluid permeability in these multi-cellular systems, finding that the resistance of fluid transport through cells controls their force-response at long times.

Mechanical properties derived from phase separation in co-polymer hydrogels.

Hydrogels can be synthesized with most of the properties needed for biomaterials applications. Soft, wettable, and highly permeable gels with a practically unlimited breadth of chemical functionalities are routinely made in the laboratory. However, the ability to make highly elastic and durable hydrogels remains limited. Here we describe an approach to generate stretchy, durable hydrogels, employing a high polymer-to-crosslink ratio for extensibility, combined with an aggregating copolymer phase to provide stability against swelling. We find that the addition of aggregating co-polymer can produce a highly extensible gel that fails at 1000% strain, recovers from large strains within a few minutes, maintains its elasticity over repeated cycles of large amplitude strain, and exhibits significantly reduced swelling. We find that the gel׳s enhanced mechanical performance comes from a kinetically arrested structure that arises from a competition between the disparate polymerization rates of the two components and the aggregation rate of the unstable phase. These results represent an alternative strategy to generating the type of stretchy elastomer-like hydrogels needed for biomedical technologies.

Polymer fluctuation lubrication in hydrogel gemini interfaces.

Interfacial sliding speed and contact pressure between the sub-units of particulate soft matter assemblies can vary dramatically across systems and with dynamic conditions. By extension, frictional interactions between particles may play a key role in their assembly, global configuration, collective motion, and bulk material properties. For example, in tightly packed assemblies of microgels - colloidal microspheres made of hydrogel - particle stiffness controls the fragility of the glassy state formed by the particles. The interplay between particle stiffness and shear stress is likely mediated by particle-particle normal forces, highlighting the potential role of hydrogel-hydrogel friction. Here we study friction at a twinned "Gemini" interface between hydrogels. We construct a lubrication curve that spans four orders of magnitude in sliding speed, and find qualitatively different behaviour from traditional lubrication of engineering material surfaces; fundamentally different types of lubrication occur at the hydrogel Gemini interface. We also explore the role played by polymer solubility and hydrogel-hydrogel adhesion in hydrogel friction. We find that polymer network elasticity, mesh size, and single-chain relaxation times can describe friction at the gel-gel interface, including a transition between lubrication regimes with varying sliding speed.

Static or breakloose friction for lubricated contacts: the role of surface roughness and dewetting.

We present experimental data for the static or breakloose friction for lubricated elastomer contacts, as a function of the time of stationary contact. Due to fluid squeeze-out from the asperity contact regions, the breakloose friction force increases continuously with the time of stationary contact. We consider three different cases: (a) PDMS rubber balls against flat smooth glass surfaces, (b) PDMS cylinder ribs against different substrates (glass, smooth and rough PMMA and an inert polymer) and (c) application to syringes. Due to differences in the surface roughness and contact pressures the three systems exhibit very different time dependences of the breakloose friction. In case (a) for rough surfaces the dry contact area A is a small fraction of the nominal contact area A0, and the fluid squeeze-out is fast. In case (b) the dry contact area is close to the nominal contact area, A/A0 ≈ 1, and fluid squeeze-out is very slow due to percolation of the contact area. In this case, remarkably, different fluids with very different viscosities, ranging from 0.005 Pa s (water­glycerol mixture) to 1.48 Pa s (glycerol), give very similar breakloose friction forces as a function of the time of stationary contact. In case (c) the contact pressure and the surface roughness are larger than in case (b), and the squeeze-out is very slow so that even after a very long time the area of real contact is below the percolation threshold. For all cases (a)­(c), the increase in the breakloose friction is mainly due to the increase in the area of real contact with increasing time, because of the fluid squeeze-out and dewetting.

Adhesion: role of bulk viscoelasticity and surface roughness.

We study the adhesion between smooth polydimethylsiloxane (PDMS) rubber balls and smooth and rough poly(methyl methacrylate) (PMMA) surfaces, and between smooth silicon nitride balls and smooth PDMS surfaces. From the measured viscoelastic modulus of the PDMS rubber we calculate the viscoelastic contribution to the crack-opening propagation energy γeff(v,T) for a wide range of crack tip velocities v and for several temperatures T. The Johnson-Kendall-Roberts (JKR) contact mechanics theory is used to analyze the ball pull-off force data, and γeff(v,T) is obtained for smooth and rough surfaces. We conclude that γeff(v,T) has contributions of similar magnitude from both the bulk viscoelastic energy dissipation close to the crack tip, and from the bond-breaking process at the crack tip. The pull-off force on the rough surfaces is strongly reduced compared to that of the flat surface, which we attribute mainly to the decrease in the area of contact on the rough surfaces.

Elastic contact mechanics: percolation of the contact area and fluid squeeze-out.

The dynamics of fluid flow at the interface between elastic solids with rough surfaces depends sensitively on the area of real contact, in particular close to the percolation threshold, where an irregular network of narrow flow channels prevails. In this paper, numerical simulation and experimental results for the contact between elastic solids with isotropic and anisotropic surface roughness are compared with the predictions of a theory based on the Persson contact mechanics theory and the Bruggeman effective medium theory. The theory predictions are in good agreement with the experimental and numerical simulation results and the (small) deviation can be understood as a finite-size effect. The fluid squeeze-out at the interface between elastic solids with randomly rough surfaces is studied. We present results for such high contact pressures that the area of real contact percolates, giving rise to sealed-off domains with pressurized fluid at the interface. The theoretical predictions are compared to experimental data for a simple model system (a rubber block squeezed against a flat glass plate), and for prefilled syringes, where the rubber plunger stopper is lubricated by a high-viscosity silicon oil to ensure functionality of the delivery device. For the latter system we compare the breakloose (or static) friction, as a function of the time of stationary contact, to the theory prediction.

Cell friction.

Cells sense and respond to their environment. Mechanotransduction is the process by which mechanical forces, stress, and strains are converted into biochemical signals that control cell behavior. In recent decades it has been shown that appropriate mechanical signals are essential to tissue health, but the role of friction and direct contact shearing across cell surfaces has been essentially unexplored. This, despite the obvious existence of numerous biological tissues whose express function depends on sliding contacts. In our studies on frictional interactions of corneal cells we find that the friction coefficients are on the order of mu = 0.03-0.06 for in vitro and in vivo experiments. Additionally, we observe cell death after single cycles of sliding at contact pressures estimated to be approximately 12 kPa. These experimental results suggest that frictional contact forces produce mechanical stresses and strains that are in the cellular mechanosensing ranges.

Passivation oxide controlled selective carbon nanotube growth on metal substrates.

Vertically aligned arrays of multi-wall carbon nanotubes (MWNT) are grown on Inconel 600, a nickel-based super-alloy. Using x-ray photoelectron spectroscopy (XPS) and chemical vapor deposition (CVD) growth of the MWNTs it is shown that a stable oxidation barrier is required for the stabilization of iron on the substrate and subsequent nanotube growth. This evidence for passivation oxide supported growth of MWNTs was then used to grow MWNTs on patterned oxidized substrates in a selective growth furnace. The unique advantage of this patterned growth on Inconel 600 is found to be the chromia passivation layer's electrical conductivity (measured value of 1.08 micro Omega m), creating the opportunity for low resistivity electrodes made from nanotubes. Inconel substrates with 100 microm long aligned MWNTs are demonstrated to exhibit an average resistance value of 2 Omega.

Origin of ultralow friction and wear in ultrananocrystalline diamond.

The impressively low friction and wear of diamond in humid environments is debated to originate from either the stability of the passivated diamond surface or sliding-induced graphitization/rehybridization of carbon. We find ultralow friction and wear for ultrananocrystalline diamond surfaces even in dry environments, and observe negligible rehybridization except for a modest, submonolayer amount under the most severe conditions (high load, low humidity). This supports the passivation hypothesis, and establishes a new regime of exceptionally low friction and wear for diamond.