High-concentration (>100 g/L) solutions of monoclonal antibodies (mAbs) are typically characterized by anomalously large solution viscosity and shear thinning behavior for strain rates ≥103 s-1. Here, the link between protein-protein interactions (PPIs) and the rheology of concentrated solutions of COE-03 and COE-19 mAbs is studied by means of static and dynamic light scattering and microfluidic rheometry. By comparing the experimental data with predictions based on the Baxter sticky hard-sphere model, we surprisingly find a connection between the observed shear thinning and the predicted percolation threshold. The longest shear relaxation time of mAbs was much larger than that of model sticky hard spheres within the same region of the phase diagram, which is attributed to the anisotropy of the mAb PPIs. Our results suggest that not only the strength but also the patchiness of short-range attractive PPIs should be explicitly accounted for by theoretical approaches aimed at predicting the shear rate-dependent viscosity of dense mAb solutions.

Field-induced reorientation of colloidal particles is especially relevant to manipulate the optical properties of a nanomaterial for target applications. We have recently shown that surprisingly feeble external stimuli are able to transform uniaxial nematic liquid crystals (LCs) of cuboidal particles into biaxial nematic LCs. In light of these results, here we apply an external field that forces the reorientation of colloidal cuboids in nematic LCs and sparks a uniaxial-to-biaxial texture switching. By dynamic Monte Carlo simulation, we investigate the unsteady-state reorientation dynamics at the particle scale when the field is applied (uniaxial-to-biaxial switching) and then removed (biaxial-to-uniaxial switching). We detect a strong correlation between the response time, being the time taken for the system to reorient, and particle anisotropy, which spans from rod-like to plate-like geometries. Interestingly, self-dual-shaped cuboids, theoretically considered as the most suitable to promote phase biaxiality for being exactly in between prolate and oblate particles, exhibit surprisingly slow response times, especially if compared to prolate cuboids.

Colloidal cuboids have the potential to self-assemble into biaxial liquid crystal phases, which exhibit two independent optical axes. Over the last few decades, several theoretical works have predicted the existence of a wide region of the phase diagram where the biaxial nematic phase would be stable, but imposed rather strong constraints on the particle rotational degrees of freedom. In this work, we use molecular simulation to investigate the impact of size dispersity on the phase behaviour of freely-rotating hard cuboids, here modelled as self-dual-shaped nanoboards. This peculiar anisotropy, exactly in between the oblate and prolate geometry, has been proposed as the most appropriate to promote phase biaxiality. We observe that size dispersity radically changes the phase behaviour of monodisperse systems and leads to the formation of an elusive biaxial nematic phase, being found in a large region of the packing fraction vs. polydispersity phase diagram. Although our results confirm the tendencies reported in past experimental observations on colloidal dispersions of slightly prolate goethite particles, they cannot reproduce the direct isotropic-to-biaxial nematic phase transition observed in these experiments.

Inertia-induced cross-stream migration has been recently exploited for precise position of particles in confined channel flows. In this work, a three-dimensional finite volume based immersed boundary method has been developed to study the lateral migration and hydrodynamic self-assembly of neutrally-buoyant particles in pressure-driven flows. Simulation results show that, in 2D channel flows, the equilibrium position for a circular particle is closer to the centreline for larger particle Reynolds number due to the increasing flow rate, while in 3D square duct flow, the equilibrium position for a spherical particle is near a face centre and is closer to the wall for larger particle Reynolds number. Self-assembly of a pair of particles is observed in 3D square duct flows but not in 2D channel flows. Mechanisms for the self-assembly are discussed.

Molecular crowding in highly concentrated monoclonal antibody (mAb) solutions results in significant increases in viscosity, which complicates fill-finish steps and patient administration by subcutaneous injection. As viscosity measurements for optimization of the mAb formulation require significant amounts of material not always available in early development, fluorescence correlation spectroscopy (FCS) is evaluated as a potential ultra-low volume technique for viscosity measurement of high concentration protein solutions assuming the Generalised Stokes Einstein relation (GSE) remains valid. Using like-charge fluorescent tracers of different sizes, FCS provided measurements of microviscosities which were compared to the macroviscosity. After parametrising the protein concentration dependence of the viscosity by the exponential coefficient (k) of a simple exponential model, FCS derived k-values of like-size tracer to the crowder followed the same ordering as the macroviscosity derived k-values with respect to solvent conditions. Furthermore, k and the diffusion-derived protein-protein interaction parameter, kD, are linked, and, attractive conditions for mAbs result in a stronger concentration dependence of the viscosity. For tracers and crowders of like-size, a key result is negative deviations from the GSE relation are observed in presence of strong attractive interactions between crowder molecules. These data demonstrate that FCS has application to the screening of high concentration mAb solutions for formulation selection.

Spatial patterns of gene expression in living organisms orchestrate cell decisions in development, homeostasis, and disease. However, most methods for reconstructing gene patterning in 3D cell culture and artificial tissues are restricted by patterning depth and scale. We introduce a depth- and scale-flexible method to direct volumetric gene expression patterning in 3D artificial tissues, which we call "heat exchangers for actuation of transcription" (HEAT). This approach leverages fluid-based heat transfer from printed networks in the tissues to activate heat-inducible transgenes expressed by embedded cells. We show that gene expression patterning can be tuned both spatially and dynamically by varying channel network architecture, fluid temperature, fluid flow direction, and stimulation timing in a user-defined manner and maintained in vivo. We apply this approach to activate the 3D positional expression of Wnt ligands and Wnt/β-catenin pathway regulators, which are major regulators of development, homeostasis, regeneration, and cancer throughout the animal kingdom.

Dynamic light scattering has become a method of choice for measuring and quantifying weak, nonspecific protein-protein interactions due to its ease of use, minimal sample consumption, and amenability to high-throughput screening via plate readers. A procedure is given on how to prepare protein samples, carry out measurements by commonly used experimental setups including flow through systems, plate readers, and cuvettes, and analyze the correlation functions to obtain diffusion coefficient data. The chapter concludes by a theoretical section that derives and rationalizes the correlation between diffusion coefficient measurements and protein-protein interactions.

By computer simulation, we model the phase behaviour of colloidal suspensions of board-like particles under the effect of an external field and assess the still disputed occurrence of the biaxial nematic (NB) liquid crystal phase. The external field promotes the rearrangement of the initial isotropic (I) or uniaxial nematic (NU) phase and the formation of the NB phase. In particular, very weak field strengths are sufficient to spark a direct I-NB or NU-NB phase transition at the self-dual shape, where prolate and oblate particle geometries fuse into one. By contrast, forming the NB phase at any other geometry requires stronger fields and thus reduces the energy efficiency of the phase transformation. Our simulation results show that self-dual shaped board-like particles with moderate anisotropy are able to form NB liquid crystals under the effect of a surprisingly weak external stimulus and suggest a path to exploit low-energy uniaxial-to-biaxial order switching.

Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.

Recent innovations in the materials used for bioprinting have enabled transformative gains in the resolution and architecture of 3D-printed engineered tissues. We focus here on one of these innovations, reported by Lee et al., which lowers the resolution limit for printing soft biomaterials.

Ovarian cancer (OvCa) is a challenging disease to treat due to poor screening techniques and late diagnosis. There is an urgent need for additional therapy options, as patients recur in 70% of cases. The limited availability of clinical treatment options could be a result of poor predictions in early stage drug screens on standard tissue culture polystyrene (TCPS). TCPS does not capture the mechanical and biochemical cues that cells experience in vivo, which can impact how cells will respond to a drug. Therefore, an in vitro model that captures some of the microenvironment features that the cells experience in vivo could provide better insights into drug responses. In this study, we formed 3D multicellular tumor spheroids (MCTS) in microwells and encapsulated them in 3D omentum-inspired hydrogels. SKOV-3 MCTS were resistant to Paclitaxel in our 3D hydrogels compared to a monolayer on TCPS. Toward clinical application, we tested cells from patients [ovarian carcinoma ascites spheroids (OCAS)] who had been treated with Paclitaxel, and drug responses predicted by using the 3D omentum-inspired hydrogels demonstrated the lack of the Paclitaxel response of these samples. Additionally, we observed the presence of collagen production around the encapsulated SKOV-3 MCTS, but not significantly on TCPS. Our results demonstrated that our 3D omentum-inspired hydrogel is an improved in vitro drug testing platform to study the OvCa drug response for patient-derived cells and helped us identify collagen 3 as a potential driver of Paclitaxel resistance in 3D.

In the shear flow of liquid crystalline polymers (LCPs) the nematic director orientation can align with the flow direction for some materials but continuously tumble in others. The nematic dumbbell (ND) model was originally developed to describe the rheology of flow-aligning semiflexible LCPs, and flow-aligning LCPs are the focus in this paper. In the shear flow of monodomain LCPs, it is usually assumed that the spatial distribution of the velocity is uniform. This is in contrast to polymer solutions, where highly nonuniform spatial velocity profiles have been observed in experiments. We analyze the ND model, with an additional gradient term in the constitutive model, using a linear stability analysis. We investigate the separate cases of constant applied shear stress and constant applied shear rate. We find that the ND model has a transient flow instability to the formation of a spatially inhomogeneous flow velocity for certain starting orientations of the director. We calculate the spatially resolved flow profile in both constant applied stress and constant applied shear rate in start up from rest, using a model with one spatial dimension to illustrate the flow behavior of the fluid. For low shear rates flow reversal can be seen as the director realigns with the flow direction, whereas for high shear rates the director reorientation occurs simultaneously across the gap. Experimentally, this inhomogeneous flow is predicted to be observed in flow reversal experiments in LCPs.

We study the phase behaviour of colloidal suspensions of monodisperse and bidisperse hard board-like particles (HBPs) as a function of their shape anisotropy, and observe a fascinating spectrum of nematic, smectic, and columnar liquid-crystalline phases, whose formation is entirely driven by excluded volume effects. We map out the phase diagram of HBPs by gradually modifying their shape from prolate to oblate and investigate the long-range order of the resulting morphologies along the phase directors and perpendicularly to them. The intrinsic biaxial nature of these particles promotes the formation of positionally ordered biaxial phases, but does not show solid evidence that it would, per se, promote the formation of the biaxial nematic phase. Our simulations shed light on the controversial existence of the discotic smectic phase, whose layers are as thick as the minor particle dimension, which is stable in a relatively large portion of our phase diagrams. Additionally, we modify the Onsager theory to describe the isotropic-nematic phase transition of freely rotating biaxial particles as a function of the particle width, and find a relatively strong first-order signature, in excellent agreement with our simulations. In an attempt to shed light on the elusive formation of the biaxial nematic phase, we apply this theory to predict the uniaxial-biaxial nematic phase transition and confirm, again in agreement with simulations, the prevailing stability of the positionally ordered smectic phase over the orientationally ordered biaxial nematic phase. In order to understand the effect of size dispersity on the formation of the biaxial nematic phase, we investigate binary mixtures of short and long HBPs, as previously studied by a mean field theory within the restricted orientation (Zwanzig model). We observe a strong demixing at relatively large density, with an especially stable smectic phase mostly formed by long HBPs at equilibrium with an isotropic phase of mostly short HBPs. Again, no evidence of the nematic biaxial phase is detected. Preliminary simulation results seem to indicate that this behaviour changes when the system is particularly polydisperse. O5. Manipulating nematic elastomers with light Daniel Corbett School of Chemical Engineering & Analytical Science, University of Manchester, Manchester, United Kingdom Abstract Long, flexible chains with rods and spacers lead to nematic polymer melts. Crosslinking the chains leads to highly extensible nematic elastomers which combine the molecular fluidity of a rubber with the orientational ordering of a nematic liquid crystal. Nematic elastomers change shape drastically when order is lost, reversible changes of 400% are easy to achieve. If the rods are dye molecules, photons can excite them from a rod-like trans state into a bent cis conformation. The bent rods reduce the orientational order and the shape of the nematic elastomer in response to heat is duplicated by illumination. Unlike heat, light penetrates quickly, is easy to deliver remotely, and optical polarisation offers additional control over mechanics. We discuss several novel photo-mechanical effects. O6. Programming colloidal self-assembly for structural hierarchy Daniel Morphew, James Shaw, Christopher Avins, Dwaipayan Chakrabarti University of Birmingham, Birmingham, United Kingdom Abstract Self-assembly is central to life, which showcases fascinating illustrations of functional organisation, often with remarkable structural hierarchies. Next-generation synthetic materials with structural hierarchies spanning multiple length scales to rival biological complexity are thus much sought-after. While colloidal self-assembly is a promising bottom-up means for structure fabrication [1-2], programming hierarchical schemes for colloidal self-assembly faces the grand challenge of bridging hierarchies of multiple lengthand time-scales associated with structure and dynamics along complex self-assembly pathways [3]. In this contribution, I will present our recent work, which explores a generic design principle, exploiting a hierarchy of interaction strengths, to address this challenge in silico in close connection with contemporary experimental research [4]. In this work, we employed a variety of computational techniques to realize the generic design principle with triblock patchy colloidal particles and demonstrate their hierarchical self-assembly into two distinct colloidal crystals, each exhibiting a two-level structural hierarchy. In particular, we obtained cubic diamond and body-centered cubic crystals via distinct clusters of uniform size and shape, namely tetrahedra and octahedra, respectively for different designer triblock patchy particles complying with the generic design principle. Our design rules thus addressed a major challenge of assembling colloidal clusters at the first level in a self-limiting way for them to serve as uniform secondary building blocks for the next level of assembly [5]. Such a conceptual design framework opens up the prospects of pushing the frontiers colloidal self-assembly. Moreover, the design framework underpins a novel bottom-up route to much sough-after cubic diamond colloidal crystals with attractive photonic applications. References: 1. S. C. Glotzer and M. J. Solomon, Nature Mater. 6, 557 (2007). 2. L. Cademartiri and K. J. M. Bishop, Nature Mater. 14, 2 (2015). 3. D. Morphew and D. Chakrabarti, Curr. Opin. Colloid Interface Sci. 30, 70 (2017). 4. D. Morphew, J. Shaw, C. Avins, D. Chakrabarti, submitted for publication. 5. M. N. O’Brien, M. R. Jones and C. A. Mirkin, Proc. Natl. Acad. Sci. USA 113, 11717 (2016). O7. Shape segregation in molecular organisation: MD simulations and X-ray scattering Mark Sims 1,2 , Laurence Abbott 2 , John Goodby 2 , John Moore 2 1 Northumbria University, Newcastle, United Kingdom. 2 University of York, York, United Kingdom Abstract The positional order and orientational order exhibited by molecules in smectic phases give rise to materials lending themselves to a range of applications. As a result, much research has focused on structure-property relationships of smectic mesogens in order to develop materials with favourable properties for their suggested applications. One particular area of focus has been on molecules with bulky end-groups; such groups have been reported to promote a range of effects, such as stabilising or destabilising smectic phases, weakening or strengthening interlayer interactions, and stabilising or destabilising the smectic A phase relative to the smectic C phase, depending on the size and chemical composition of the end-group in question, and on the structure of the mesogen. Siloxane groups have been relatively widely studied in this context, and siloxane-terminated cyanobiphenyls have been shown to exhibit favourable properties for use in scattering devices. 1 Their properties are typically attributed to chemical incompatibility introduced by the siloxane moieties, but recent studies have indicated that similar properties may be exhibited by introducing bulky alkyl substituents, 2,3 suggesting that chemical incompatibility may not be the cause of the differences in material properties. We have carried out experimental and computational studies on the cyanobiphenyl molecules shown in Figure 1. X-ray scattering studies enabled smectic layer spacings and translational order parameters to be determined, and the experimental trends were matched by those calculated from fully atomistic MD simulations. The degrees of molecular interdigitation in the simulations were quantified and related to the sizes of the terminal groups, suggesting that “shape segregation” gives rise to significantly different layer structures between the two materials. The atomic resolution results from the MD simulations provide a data-set from which results of experimental X-ray mesurements may be understood and rationalised. Figure 1 Structures of the two molecules studied in this work (far left and right) along with snapshots of the MD simulations (middle left and right) with the aromatic and aliphatic regions coloured in purple and yellow, respectively. 1. M. Ibn-Elhaj, H. J. Coles, D. Guillon and A. Skoulios, J. Phys. II France, 1993, 3, 1807-1817. 2. R. J. Mandle, E. J. Davis, C.-C. A. Voll, D. J. Lewis, S. J. Cowling and J. W. Goodby, J. Mater. Chem. C, 2015, 3, 2380-2388. 3. J. W. Goodby, R. J. Mandle, E. J. Davis, T. Zhong and S. J. Cowling, Liq. Cryst., 2015, 42, 593-622. O8. Studying sanidic lamellar-like mesophases in conjugated polymers using a new symmetryinspired model Cristina Greco, Kurt Kremer, Kostas Daoulas Max Planck Institute for Polymer Research, Mainz, Germany Abstract In conjugated polymers, charge transport properties are known to be strongly affected by morphology. An interesting recent observation is that, to achieve high mobilities, perfect lamellar order is not necessary [1]. Here we present a simple model that enables the study of sanidic liquid crystalline mesophases characterized by partial lamellar order, at device-relevant length scales. Nonbonded interactions responsible for coplanarity in chain orientation and for stacking are described by anisotropic soft potentials constructed on the basis of simple symmetry considerations. Using polyalkylthiophenes as a test system, we perform Monte Carlo simulations of chains of various lengths. Lamellar-like morphologies are obtained, either as monoor poly-domains. The type of lamellar order is identified by computing 2D scattering patterns, which can be compared with experimental GIWAXS data. From this analysis, we conclude that our morphologies indeed reproduce an experimentaly reported liquid crystalline mesophase [2]. We analyze the organization of chains inside the lamellae and identify in a simple way connectivity pathways between lamellae. In the future, atomistic details can be reintroduced via backmapping, allowing for prediction of charge transport properties [

Colloids have a striking relevance in a wide spectrum of industrial formulations, spanning from personal care products to protective paints. Their behaviour can be easily influenced by extremely weak forces, which disturb their thermodynamic equilibrium and dramatically determine their performance. Motivated by the impact of colloidal dispersions in fundamental science and formulation engineering, we have designed an efficient Dynamic Monte Carlo (DMC) approach to mimic their out-of-equilibrium dynamics. Our recent theory, which provided a rigorous method to reproduce the Brownian motion of colloids by MC simulations, is here generalised to reproduce the Brownian motion of colloidal particles during transitory unsteady states, when their thermodynamic equilibrium is significantly modified. To this end, we investigate monodisperse and bidisperse rod-like particles in the isotropic phase and apply an external field that forces their reorientation along a common direction and induces an isotropic-to-nematic phase transition. We also study the behaviour of the system once the external field is removed. Our simulations are in excellent quantitative agreement with Brownian Dynamics simulations when the DMC results are rescaled with a time-dependent acceptance ratio, which depends on the strength of the applied field.

Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Multicellular tumor spheroids (MCTS) are a popular method for three-dimensional (3D) cell culture, because they capture some aspects of the dimensionality, cell-cell contact, and cell-matrix interactions seen in vivo. Many approaches exist to create MCTS from cell lines, and they have been used to study tumor cell invasion, growth, and how cells respond to drugs in physiologically relevant 3D microenvironments. However, there are several discrepancies in the observations made of cell behaviors when comparing between MCTS formation methods. To resolve these inconsistencies, we created and compared the behavior of breast, prostate, and ovarian cancer cells across three MCTS formation methods: in polyNIPAAM gels, in microwells, or in suspension culture. These methods formed MCTS via proliferation from single cells or passive aggregation, and therefore showed differential reliance on genes important for cell-cell or cell-matrix interactions. We also found that the MCTS formation method dictated drug sensitivity, where MCTS formed over longer periods of time via clonal growth were more resistant to treatment. Toward clinical application, we compared an ovarian cancer cell line MCTS formed in polyNIPAAM with cells from patient-derived malignant ascites. The method that relied on clonal growth (PolyNIPAAM gel) was more time and cost intensive, but yielded MCTS that were uniformly spherical, and exhibited the most reproducible drug responses. Conversely, MCTS methods that relied on aggregation were faster, but yielded MCTS with grapelike, lobular structures. These three MCTS formation methods differed in culture time requirements and complexity, and had distinct drug response profiles, suggesting the choice of MCTS formation method should be carefully chosen based on the application required.

We have characterised the flow of semi-dilute PAAm solutions (3.3c* <= c <= 16.6c*) through a threedimensional cross-slot device (width to depth aspect ratio 2: 1) over a range of Weissenberg (0.13 <= Wi <= 88.5) and Elasticity (1.5 <= El <= 58.4) numbers by means of micro-particle imaging velocimetry (mu-PIV) and pressure drop measurements. The flow regimes are mapped into a Wi Re diagram. At intermediate Wi (12 <= Wi <= 45) we observe the formation of lip vortices in the inlet channels. At higher Wi (Wi >= 45) we observe the onset of an asymmetric flow regime, which occurs at a much higher Weissenberg number than previously reported in the literature. Increasing El in the asymmetric flow regime results in flow patterns that are markedly more time-dependent and unstable. The extensional rates measured along the centreline of the outlet channels are much lower than the corresponding nominal values. By means of an improved version of the numerical method that was used in our previous works, we have linked the measured velocity field with the "local Deborah number" field to quantify the spatial distribution of the deformation rate underwent by the polymer chains at high Wi flows near the stagnation point of the cross slot device. We measured the extensional viscosity and Trouton ratios of our polymer solutions over a range of 1 <= Wi <= 30. This work is of significance for the development of extensional rheometers for measuring the properties of low-viscosity fluids such as inks, blood, silk fibroin and protein solutions. (C) 2017 Elsevier B.V. All rights reserved.

The thread running through this book is the conversion of light into molecular transformations (on the nanoscale) and thence into mechanical distortions on the macroscopic scale. One is aiming for optoactuation, for the conversion of light energy into alternative forms, or for optically driven elements for more complex devices. The molecules being transformed by light should be in their solid phases in order for light energy to be transduced. The solids investigated are crystals, amorphous (glassy, polydomain, or plastic) solids, orientationally ordered glasses and elastomers, and even classic elastomers. The common element is the photochromic entity that suffers a shape change upon excitation by photon absorption–as discussed by Barrett in Chapter 2. Molecular shape change, most typically from rod-like to bent, intuitively suggests a reduction in packing efficiency and hence a dilation of the solid. Either the photochromics are the single species present, or they are present as guests in the solid matrix. Either way, if the solid (eg, a molecular crystal) has the photochromics directionally ordered, then the contribution to the creation of free volume along and perpendicular to the preferred direction will be different and so, on top of a background level of isotropic swelling, there will be directionally dependent distortion. For solids such as crystals, glasses, and composites, the picture seems apposite and the responses are large (2–10% strain) compared with conventional thermal response in solids, but small compared with those of photoresponsive elastomers (20–400% strain). To our knowledge, there are no quantitative, mechanistic pictures for the …