Intrinsic nonlinearities in the mechanics of hard sphere suspensions.

The onset of nonlinear responses in near hard sphere suspensions is characterized as a function of oscillatory frequency and strain amplitude. At low frequencies where the viscous behavior dominates, the onset of nonlinearities is driven by increases in rate of strain. At high deformation frequency, where suspension mechanics is dominated by an elastic response, the nonlinear responses occur when deformation exceeds a characteristic strain. This strain is associated with the transient confinement of particles by nearest neighbors and its volume fraction dependence is through cage parameters derived from the high frequency elastic modulus. The onset of nonlinear responses takes on a universal behavior when deformation frequency is normalized by the characteristic time governing the shift from viscous to elastic behavior indicating that this transition is associated with transient particle localization and is expected to be observed for all volume fractions where pair interactions are important.

Gelation of Fmoc-diphenylalanine is a first order phase transition.

We explore the gel transition of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). The addition of water to a solution of Fmoc-FF in dimethyl sulfoxide (DMSO) results in increased attractions leading to self-assembly of Fmoc-FF molecules into a space-filling fibrous network. We provide evidence that gel formation is associated with a first order phase transition resulting in nucleation and growth of strongly anisotropic crystals with high aspect ratios. The strength of attraction between Fmoc-FF molecules as a function of water concentration is estimated from long-time self-diffusion measurements using (1)H NMR diffusion-ordered spectroscopy (DOSY). The resulting phase behavior follows that observed for a wide range of other crystallizing nanoparticles and small molecules - a result consistent with the short-range nature of the intermolecular attractions. Furthermore, we use NMR to measure the rate of increase in the fraction of bound Fmoc-FF molecules after water is suddenly mixed into the system. We observe a lag time in the formation of the new phase indicative of the existence of a free energy barrier to the formation of a crystal nucleus of critical size. The application of classical nucleation theory for a cylindrical nucleus indicates that one-dimensional crystal growth is driven by an imbalance of the surface energies of the ends and sides of the fiber.

Impact of small changes in particle surface chemistry for unentangled polymer nanocomposites.

We report microstructural and rheological consequences of altering silica particle surface chemistry when the particles are suspended in unentangled polyethylene glycol with a molecular weight of 400. The particle surfaces are altered by reacting them with isobutyltrimethyoxysilane. Levels of silanization are chosen so that the particles remain dispersed in the polymer at all volume fractions studied. Our studies indicate that at the levels studied, silanization does not alter the hydrodynamic thickness of the absorbed polymer layer thickness. Rheological properties are not sensitive to levels of silanization up to particle volume fractions where the average particle separation h ∼ 6Rg (4.8 nm). At these volume fractions, composite microstructure undergoes changes associated with jamming of soft particles (decorrelations in the first peak of the particle structure factor and the onset of a non-diffusive mechanism that dominates particle density fluctuations at short times.) In the region of volume fractions where h/Rg < 6, the zero-shear rate viscosity of the composites is extremely sensitive to level of silanization with a decrease in the zero-shear rate viscosity by four orders of magnitude observed for the highest levels of silanization studied in comparison to the bare particles.

Mechanical properties of self-assembled Fmoc-diphenylalanine molecular gels.

We explore the phase diagram and mechanical properties of molecular gels produced from mixing water with a dimethyl sulfoxide (DMSO) solution of the aromatic dipeptide derivative fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). Highly soluble in DMSO, Fmoc-FF assembles into fibrous networks that form gels upon addition of water. At high water concentrations, rigid gels can be formed at Fmoc-FF concentrations as low as 0.01 wt %. The conditions are established defining the Fmoc-FF and water concentrations at which gels are formed. Below the gel boundary, the solutions are clear and colorless and have long-term stability. Above the gel boundary, gels are formed with increasing rapidity with increasing water or Fmoc-FF concentrations. A systematic characterization of the effect of Fmoc-FF and water concentrations on the mechanical properties of the gels is presented, demonstrating that the elastic behavior of the gels follows a specific, robust scaling with Fmoc-FF volume fraction. Furthermore, we characterize the kinetics of gelation and demonstrate that these gels are reversible in the sense that they can be disrupted mechanically and rebuild strength over time.

Binary diamondoid building blocks for molecular gels.

Adamantane is a type of diamondoid molecules that has a cage or globular shape with a diameter of 6.34 ± 0.04 Å.8 Anisotropic interactions between these truly nanoscopic particles can be induced through the derivatization of the diamondoid cage. Here we explore the gelation of paired systems of adamantane where attractions are introduced through van der Waals forces and hydrogen bonding. Gels are produced through the mixing of 1-adamantanecarboxylic acid (A1C) and 1-adamantylamine (A1N). Upon mixing dimethyl sulfoxide solutions of these molecules at vanishing concentrations, these diamondoid molecules rapidly precipitate. A space-filling gel of the resulting aggregates is observed at approximately 3% by weight. These resulting gels have elastic moduli of 10(2)-10(4) Pa in the 3-7 wt % concentration range. At a 1:1 mol ratio of 1-adamantanecarboxylic acid (A1C) and 1-adamantylamine (A1N), the gel's elastic modulus and yield stress increase as volume fractions ϕ(x) and ϕ(y) with x ≈ 4.2 and y ≈ 3.5. The dependencies of moduli and yield stress on the volume fraction display characteristics of colloidal gels. Transmission electron microscope (TEM) images indicate that the gels are formed from a network of interwoven and branched fibers which are composed of ∼30 nm crystallites that have undergone oriented aggregation to form fibers.

Evidence for equilibrium gels of valence-limited particles.

We explore the formation and structure of gels produced from solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide (DMSO). Mixing these solutions with water results in the self-assembly of Fmoc-FF molecules into space-filling fibrous networks, exhibiting mechanical properties characteristic of gels. Using confocal fluorescence microscopy, we observe the gel transition in situ and find that, upon the addition of water, the solution undergoes a rapid transition to a non-equilibrium state forming ∼ 2 µm spheres, followed by the formation of fibers 5-10 nm in diameter, nucleating at a sphere surface and expanding into the solution as the remaining spheres dissolve, extending the network. The gel aging process is associated with the network becoming increasingly uniform through apparent redissolution/reaggregation of the Fmoc-FF molecules, corresponding to the observed increase in the elastic modulus to a plateau value. We demonstrate that this increase in uniformity and elastic modulus can be expedited by controlling the temperature of the system, as well as that these gels are thermally reversible, further indicating that the system is in equilibrium in its fibrous network state. X-ray scattering information suggests that the packing of the molecules within a fiber is based on π-π stacking of ß-sheets, consistent with models proposed in the literature for similar systems, implying that each particle (molecule) possesses a limited number of interaction sites. These observations provide experimental evidence that these low molecular weight gelator molecules can be considered valence-limited "patchy" particles, which associate at low enough temperature to form equilibrium gels.

Nanoscale dynamics and aging of fibrous peptide-based gels.

Solutions of the aromatic dipeptide derivative molecule fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) in dimethyl sulfoxide produce fibrous gels when mixed with water. We study the evolution of density fluctuations of this three-component system using X-ray photon correlation spectroscopy (XPCS) and compare these results to the macroscopic rheology of the gels and optical observations of the microstructure evolution. At the investigated scattering angles, the intensity autocorrelation functions do not follow behavior expected for simple diffusion of individual Fmoc-FF molecules localized within cages of nearest neighbors. Instead, the dynamics are associated with density fluctuations on length scales of ~10-100 nm arising from disaggregation and reformation of fibers, leading to an increasingly uniform network. This process is correlated with the growth of the elastic modulus, which saturates at long times. Autocorrelation functions and relaxation times acquired from XPCS measurements are consistent with relaxation rates of structures at dynamic equilibrium. This study provides further support to the concept of exploring peptide-based gelators as valence-limited patchy particles capable of forming equilibrium gels.

Grand Challenges at the Interface of Engineering and Medicine.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating "avatars" (herein defined as an extension of "digital twins") of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Synthesis of pH-responsive particles with shape anisotropy.

Seeded emulsion polymerization is used to produce large quantities of shape anisotropic, amphoteric particles in a size range of about 1 µm. Copolymer dicolloids (CDCs) containing pyridine groups are synthesized by swelling spherical, lightly cross-linked polystyrene seeds with a mixture of styrene and pH-responsive monomer 2-vinyl pyridine followed by secondary polymerization to contrast with their analogue homopolymer dicolloids (HDCs) where the swelling step is carried out with styrene alone. After the particles are coated with a nonionic surfactant to minimize van der Waals attractions, surface potentials and aggregation properties of dilute suspensions are studied as functions of pH and ionic strength. Compared to HDCs, which remain stable at all pH values studied (3 < pH < 9) up to an ionic strength of 5 M, the CDC particles show amphoteric behavior with strong attractions under conditions where dipolar interactions are expected to dominate.

Effect of the range of repulsions on the existence of a stable liquid phase.

Experimental and theoretical results have established that the range of the attraction plays a critical role in determining whether a particle system exhibits a stable liquid phase. Changes to the range of the repulsions can similarly affect the existence of a stable liquid phase; however, these effects have not been clearly elucidated. We demonstrate that an increase in the range of repulsions can either enhance or decrease the stability of the liquid phase, depending on the form of the interaction potential. For either case, the critical variable that controls the stability of the liquid phase is the ratio of the representative energies of the liquid and solid phases.

Small-angle X-ray scattering studies of the intact eye lens: effect of crystallin composition and concentration on microstructure.

BACKGROUND: The cortex and nucleus of eye lenses are differentiated by both crystallin protein concentration and relative distribution of three major crystallins (alpha, beta, and gamma). Here, we explore the effects of composition and concentration of crystallins on the microstructure of the intact bovine lens (37 degrees C) along with several lenses from Antarctic fish (-2 degrees C) and subtropical bigeye tuna (18 degrees C). METHODS: Our studies are based on small-angle X-ray scattering (SAXS) investigations of the intact lens slices where we study the effect of crystallin composition and concentration on microstructure. RESULTS: We are able to distinguish the nuclear and cortical regions by the development of a characteristic peak in the intensity of scattered X-rays. For both the bovine and fish lenses, the peak corresponds to that expected for dense suspensions of alpha-crystallins. CONCLUSIONS: The absence of the scattering peak in the nucleus indicates that there is no characteristic wavelength for density fluctuations in the nucleus although there is liquid-like order in the packing of the different crystallins. The loss in peak is due to increased polydispersity in the sizes of the crystallins and due to the packing of the smaller gamma-crystallins in the void space of alpha-crystallins. GENERAL SIGNIFICANCE: Our results provide an understanding for the low turbidity of the eye lens that is a mixture of different proteins. This will inform design of optically transparent suspensions that can be used in a number of applications (e.g., artificial liquid lenses) or to better understand human diseases pathologies such as cataract.

Multiscale structure, interfacial cohesion, adsorbed layers, and thermodynamics in dense polymer-nanoparticle mixtures.

We establish the existence and size of adsorbed polymer layers in miscible dense nanocomposites and their consequences on microstructure and the bulk modulus. Using contrast-matching small-angle neutron scattering to characterize all partial collective structure factors of polymers, particles, and their interface, we demonstrate qualitative failure of the random phase approximation, accuracy of the polymer reference site interaction model theory, ability to deduce the adsorbed polymer layer thickness, and high sensitivity of the nanocomposite bulk modulus to interfacial cohesion.

Role of polymer segment-particle surface interactions in controlling nanoparticle dispersions in concentrated polymer solutions.

The microstructure of particles suspended in concentrated polymer solutions is examined with small-angle X-ray scattering and small-angle neutron scattering. Of interest are changes to long wavelength particle density fluctuations in ternary mixtures of silica nanoparticles suspended in concentrated solutions of poly(ethylene glycol). The results are understood in terms of application of the pseudo-two-component polymer reference interaction site model (PRISM) theory modified to account for solvent addition via effective contact strength of interfacial attraction, ε(pc), in an implicit manner. The combined experimental-theoretical study emphasizes the complex interactions between solvent, polymer, and particle surface that control particle miscibility but also demonstrate that these factors can all be understood in terms of variations of ε(pc).

Particle restabilization in silica/PEG/ethanol suspensions: how strongly do polymers need to adsorb to stabilize against aggregation?

We study the effects of increasing the concentration of a low molecular weight polyethylene glycol on the stability of 44 nm diameter silica nanoparticles suspended in ethanol. Polymer concentration, c(p), is increased from zero to that characterizing the polymer melt. Particle stability is accessed through measurement of the particle second-virial coefficient, B(2), performed by light scattering and ultrasmall angle X-ray scattering (USAXS). The results show that at low polymer concentration, c(p) < 3 wt %, B(2) values are positive, indicating repulsive interactions between particles. B(2) decreases at intermediate concentrations (3 wt % < c(p) < 50 wt %), and particles aggregates are formed. At high concentrations (50 wt % < c(p)) B(2) increases and stabilizes at a value expected for hard spheres with a diameter near 44 nm, indicating the particles are thermodynamically stable. At intermediate polymer concentrations, rates of aggregation are determined by measuring time-dependent changes in the suspension turbidity, revealing that aggregation is slowed by the necessity of the particles diffusing over a repulsive barrier in the pair potential. The magnitude of the barrier passes through a minimum at c(p) ≈ 12 wt % where it has a value of ∼12 kT. These results are understood in terms of a reduction of electrostatic repulsion and van der Waals attractions with increasing c(p). Depletion attractions are found to play a minor role in particle stability. A model is presented suggesting displacement of weakly adsorbed polymer leads to slow aggregation at intermediate concentration, and we conclude that a general model of depletion restabilization may involve increased strength of polymer adsorption with increasing polymer concentration.

Re-entrant kinetic arrest and elasticity of concentrated suspensions of spherical and nonspherical repulsive and attractive colloids.

We have designed and studied a new experimental colloidal system to probe how the weak shape anisotropy of uniaxial particles and variable repulsive (Coulombic) and attractive (van der Waals) forces influence slow dynamics, shear elasticity, and kinetic vitrification in dense suspensions. The introduction of shape anisotropy dramatically delays kinetic vitrification and reduces the shear elastic modulus of colloidal diatomics relative to their chemically identical spherical analogs. Tuning the interparticle interaction from repulsive, to nearly hard, to attractive by increasing suspension ionic strength reveals a nonmonotonic re-entrant dynamical phase behavior (glass-fluid-gel) and a rich variation of the shear modulus. The experimental results are quantitatively confronted with recent predictions of ideal mode coupling and activated barrier hopping theories of kinetic arrest and elasticity, and good agreement is generally found with a couple of exceptions. The systems created may have interesting materials science applications such as flowable ultrahigh volume fraction suspensions, or responsive fluids that can be reversibly switched between a flowing liquid and a solid nonequilibrium state based on in situ modification of suspension ionic strength.

Yielding in dense suspensions: cage, bond, and rotational confinements.

The effect of weak particle anisotropy on the onset of fluidity in dense suspensions of glasses of repulsive, weakly attractive and strongly attractive spherical and dumbbell shaped particles is explored. Yield stresses are found to scale with volume fraction showing a divergence at random close packing for all systems. However the onsets of yielding in suspensions of spherical and dumbbell shaped particles are shown to display qualitatively different behaviors. Suspensions of hard spheres exhibit a single yield stress (strain) while suspensions of spheres experiencing short range attractions in dense gels display two yielding events. Double yielding occurs when attractions between particles are only a few kT and the suspensions are sufficiently dense. For dumbbell suspensions, single yielding is observed for hard dumbbell glasses in a region where the glasses are expected to be plastic while double yielding is observed when the particles are expected to have localized centers of mass and localized orientations. Double yielding is also observed for dense dumbbell suspensions that experience attractions while only single yielding events are observed in strongly attractive gels for both dumbbells and spheres. These results are discussed in the light of recent theories and simulations of mechanisms of localization in suspensions of spherical and weakly anisotropic particles.

Rheology and microstructure of polymer nanocomposite melts: variation of polymer segment-surface interaction.

We have studied the effects of particle packing fraction, polymer molecular weight (MW), and polymer-segment-particle-surface affinity on the phase behavior of 44 nm silica dispersions in unentangled, low MW polyethylene oxide (PEO), polyethylene oxide dimethyl ether (PEODME), and polytetrahydrofuran (PTHF) through rheological measurement and small-angle X-ray scattering. Particles are shown to be stable in PEO nanocomposites up to high volume fractions due to an adsorbed layer of polymer segments that stabilizes particles in the melt. Comparison of the PEO nanocomposite to PEODME and PTHF nanocomposites reveals little evidence of an adsorbed layer in the spirit of the PEO nanocomposite. Measurement of the PTHF nanocomposite viscosity reveals evidence of segment slip at the particle surface by the particle intrinsic viscosity being less than Einstein's value. At higher particle volume fractions, the viscosity diverges, yielding an elastic response. The elastic response of the PEO nanocomposite has the signatures of a colloidal glass, while the PEODME and PTHF nanocomposites resemble a gel. Measurement of the particle structure factor reveals a change from overall repulsive particles in PEO to attractive particles in PTHF as the segment-surface interaction is changed.

Emulsion polymerization routes to chemically anisotropic particles.

Methods are presented to synthesize suspensions of chemically and shape anisotropic colloids on submicrometer length scales. Particles are synthesized through seeded emulsion polymerization where a weakly cross-linked seed is swollen with monomer that phase separates at the reaction temperature resulting in a protrusion. The final particles can be considered to be composed of interpenetrating spheres. pH-sensitive anisotropy is created through the use of different surface coatings on each of the interpenetrating spheres. Dark-field imaging, dynamic light scattering, and scanning electron microscopy are used to characterize the particles.

Colloidal glass transition in unentangled polymer nanocomposite melts.

The linear and non-linear rheology of a high volume fraction particle filled unentangled polymer melt is measured. The particles in the polymer melt behave like hard spheres as the particle volume fraction is raised. At high volume fractions, the suspension develops a plateau elastic modulus. Over the frequency range of the elastic modulus plateau, the viscous modulus develops a minimum and a maximum. The frequencies of the two local extrema initially have critical power law scaling, suggesting the approach of a singular glass transition. At higher volume fractions in excess of the glass transition, the viscous modulus continues to show a well defined minimum and a well defined maximum. The non-linear moduli show a single perturbative yield point beyond which the suspension softens. The yielding behavior of the nanocomposite is shown to be sensitive to the strain frequency and the proximity of the strain frequency to the maximum frequency for the linear viscous modulus from linear rheology which characterizes thermal relaxation of glassy particle clusters in the zero strain limit. The linear and non-linear measurements are compared against a recently developed mechanical theory for colloidal glasses.

Self-assembly pathways and polymorphism in peptide-based nanostructures.

Dipeptide derivative molecules can self-assemble into space-filling nanofiber networks at low volume fractions (<1%), allowing the formation of molecular gels with tunable mechanical properties. The self-assembly of dipeptide-based molecules is reminiscent of pathological amyloid fibril formation by naturally occurring polypeptides. Fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) is the most widely studied such molecule, but the thermodynamic and kinetic phenomena giving rise to Fmoc-FF gel formation remain poorly understood. We have previously presented evidence that the gelation process is a first order phase transition characterized by low energy barriers to nucleation, short induction times, and rapid quasi-one-dimensional crystal growth, stemming from solvent-solute interactions and highly specific molecular packing. Here, we discuss the phase behavior of Fmoc-FF in different solvents. We find that Fmoc-FF gel formation can be induced in apolar solvents, in addition to previously established pathways in aqueous systems. We further show that in certain solvent systems anisotropic crystals (nanofibers) are an initial metastable state, after which macroscopic crystal aggregates with no preferred axis of growth are formed. The molecular conformation is sensitive to solvent composition during assembly, indicating that Fmoc-FF may be a simple model system to study complex thermodynamic and kinetic phenomena involved in peptide self-assembly.