Wrapping anisotropic microgel particles in lipid membranes: Effects of particle shape and membrane rigidity.

Cellular engulfment and uptake of macromolecular assemblies or nanoparticles via endocytosis can be associated to both healthy and disease-related biological processes as well as delivery of drug nanoparticles and potential nanotoxicity of pollutants. Depending on the physical and chemical properties of the system, the adsorbed particles may remain at the membrane surface, become wrapped by the membrane, or translocate across the membrane through an endocytosis-like process. In this paper, we address the question of how the wrapping of colloidal particles by lipid membranes can be controlled by the shape of the particles, the particle-membrane adhesion energy, the membrane phase behavior, and the membrane-bending rigidity. We use a model system composed of soft core-shell microgel particles with spherical and ellipsoidal shapes, together with phospholipid membranes with varying composition. Confocal microscopy data clearly demonstrate how tuning of these basic properties of particles and membranes can be used to direct wrapping and membrane deformation and the organization of the particles at the membrane. The deep-wrapped states are more favorable for ellipsoidal than for spherical microgel particles of similar volume. Theoretical calculations for fixed adhesion strength predict the opposite behavior-wrapping becomes more difficult with increasing aspect ratio. The comparison with the experiments implies that the microgel adhesion strength must increase with increasing particle stretching. Considering the versatility offered by microgels systems to be synthesized with different shapes, functionalizations, and mechanical properties, the present findings further inspire future studies involving nanoparticle-membrane interactions relevant for the design of novel biomaterials and therapeutic applications.

Charged hollow microgel capsules.

Responsive hollow microgels are a fascinating class of soft model systems at the crossover between polymer capsules and microgels. The presence of the cavity makes them promising materials for encapsulation and controlled release applications but also confers them an additional softness that is reflected by their peculiar behaviour in bulk and at interfaces. Their responsivity to external stimuli, such as temperature, pH, and ionic strength, can be designed from their synthesis conditions and the choice of functional moieties. So far most studies have focused on "small" hollow microgels that were mostly studied with scattering or atomic force microscopy techniques. In our previous study, we have shown that large fluorescent hollow poly(N-isopropylacrylamide) (PNIPAM) microgels could be synthesized using micrometer-sized silica particles as sacrificial templates allowing their investigation in situ via confocal microscopy. In this work, we extend this approach to charged large hollow microgels based on poly(N-isopropylacrylamide-co-itaconic acid) (P(NIPAM-co-IA)). Hereby, we compare the structure and responsivity of "neutral" (PNIPAM) and "charged" (P(NIPAM-co-IA)) hollow microgel systems synthesized under similar conditions with the same sacrificial template using confocal and atomic force microscopy and light scattering techniques. In particular, we could demonstrate the extremely soft character of the swollen charged hollow microgels and their responsivity to pH, ionic strength, and temperature. To conclude this study, the buckling behavior of the different capsules was investigated illustrating the potential of such systems to change its conformation by varying the osmotic pressure and pH conditions.

How Softness Matters in Soft Nanogels and Nanogel Assemblies.

Softness plays a key role in determining the macroscopic properties of colloidal systems, from synthetic nanogels to biological macromolecules, from viruses to star polymers. However, we are missing a way to quantify what the term "softness" means in nanoscience. Having quantitative parameters is fundamental to compare different systems and understand what the consequences of softness on the macroscopic properties are. Here, we propose different quantities that can be measured using scattering methods and microscopy experiments. On the basis of these quantities, we review the recent literature on micro- and nanogels, i.e. cross-linked polymer networks swollen in water, a widely used model system for soft colloids. Applying our criteria, we address the question what makes a nanomaterial soft? We discuss and introduce general criteria to quantify the different definitions of softness for an individual compressible colloid. This is done in terms of the energetic cost associated with the deformation and the capability of the colloid to isotropically deswell. Then, concentrated solutions of soft colloids are considered. New definitions of softness and new parameters, which depend on the particle-to-particle interactions, are introduced in terms of faceting and interpenetration. The influence of the different synthetic routes on the softness of nanogels is discussed. Concentrated solutions of nanogels are considered and we review the recent results in the literature concerning the phase behavior and flow properties of nanogels both in three and two dimensions, in the light of the different parameters we defined. The aim of this review is to look at the results on micro- and nanogels in a more quantitative way that allow us to explain the reported properties in terms of differences in colloidal softness. Furthermore, this review can give researchers dealing with soft colloids quantitative methods to define unambiguously which softness matters in their compound.

How the interplay of molecular and colloidal scales controls drying of microgel dispersions.

Bringing an aqueous dispersion or solution into open air leads to water evaporation. The resulting drying process initiates the buildup of spatial heterogeneities, as nonvolatile solutes and colloids concentrate. Such composition gradients associate with mesostructure gradients, which, in turn, impact flows within these multicomponent systems. In this work, we investigate the drying of microgel dispersions in respect to two reference systems, a colloidal dispersion and a polymer solution, which, respectively, involve colloidal and molecular length scales. We evidence an intermediate behavior in which a film forms at the air/liquid interface and is clearly separated from bulk by a sharp drying front. However, complex composition and mesostructure gradients develop throughout the drying film, as evidenced by Raman and small-angle X-ray scattering mapping. We show that this results from the soft colloidal structure of microgel, which allows them to interpenetrate, deform, and deswell. As a result, water activity and water transport are drastically decreased in the vicinity of the air/liquid interface. This notably leads to diffusional drying kinetics that are nearly independent on the air relative humidity. The interplay between water fraction, water activity, and mesostructure on water transport is generic and, thus, shown to be pivotal in order to master evaporation in drying complex fluids.

Thermally and Magnetically Programmable Hydrogel Microactuators.

The rapid development in micro-machinery enabled the investigation of smart materials that can embody fast response, programmable actuation, and flexibility to perform mechanical work. Soft magnetic actuators represent an interesting platform toward combining those properties. This study focuses on the synthesis of micro-actuators that respond to thermal and magnetic stimuli using micro-molding with a soft template as a fabrication technique. These microsystems consist of a hydrogel matrix loaded with anisotropic magnetic nanospindles. When a homogeneous magnetic field is applied, the nanospindles initially dispersed in monomer solution, align and assemble into dipolar chains. The ensuing UV-polymerization creates a network and conveniently arrests these nanostructures. Consequently, the magnetic dipole moment is coplanar with the microgel. Varying the shape, volume, and composition of the micro-actuators during synthesis provides a temperature-dependent control over the magnetic response and the polarizability. Beyond isotropic swelling, shaping the hydrogel as long thin ribbons with a passive layer on one side allows for differential swelling leading to bending and twisting deformations, for example, 2D- or 3D-spiral. These deformations involve a reversible amplification of the magnetic response and orientation of the hydrogels under magnetic field. Temperature control herewith determines the conformation and simultaneously the magnetic response of the micro-actuators.

Interfacial Assembly of Anisotropic Core-Shell and Hollow Microgels.

Microgels, cross-linked polymers with submicrometer size, are ideal soft model systems. While spherical microgels have been studied extensively, anisotropic microgels have hardly been investigated. In this study, we compare the interfacial deformation and assembly of anisotropic core-shell and hollow microgels. The core-shell microgel consists of an elliptical core of hematite covered with a thin silica layer and a thin shell made of poly(N-isopropylacrylamide). The hollow microgels were obtained after a two-step etching procedure of the inorganic core. The behavior of these microgels at the oil-water interface was investigated in a Langmuir-Blodgett trough combined with ex situ atomic force microscopy. First, the influence of the architecture of anisotropic microgels on their spreading at the interface was investigated experimentally and by dissipative particle dynamic simulations. Hereby, the importance of the local shell thickness on the lateral and longitudinal interfacial deformation was highlighted as well as the differences between the core-shell and hollow architectures. The shape of the compression isotherms as well as the dimensions, ordering, and orientation of the microgels at the different compressions were analyzed. Due to their anisotropic shape and stiffness, both anisotropic microgels were found to exhibit significant capillary interactions with a preferential side-to-side assembly leading to stable microgel clusters at low interfacial coverage. Such capillary interactions were found to decrease in the case of the more deformable hollow anisotropic microgels. Consequently, anisotropic hollow microgels were found to distribute more evenly at high surface pressure compared to stiffer core-shell microgels. Our findings emphasize the complex interplay between the colloid design, anisotropy, and softness on the interfacial assembly and the opportunities it therefore offers to create more complex ordered interfaces.

Anisotropic Microgels Show Their Soft Side.

Anisotropic, submicrometer-sized particles are versatile systems providing interesting features in creating ordering in two-dimensional systems. Combining hard ellipsoids with a soft shell further enhances the opportunities to trigger and control order and alignment. In this work, we report rich 2D phase behavior and show how softness affects the ordering of anisotropic particles at fluid oil-water interfaces. Three different core-shell systems were synthesized such that they have the same elliptical hematite-silica core but differ with respect to thickness and stiffness of the soft microgel shell. Compression isotherms, the shape of individual core-shell microgels, and their 2D order at a decane-water interface are investigated by means of the Langmuir-Blodgett technique combined with ex-situ atomic force microscopy (AFM) imaging as well as dissipative particle dynamics (DPD) simulations. We show how the softness, size, and anisotropy of the microgel shell affect the side-to-side vs tip-to-tip ordering of anisotropic hybrid microgels as well as the alignment with respect to the direction of compression in the Langmuir trough. A large, soft microgel shell leads to an ordered structure with tip-to-tip alignment directed perpendicular to the direction of compression. In contrast, a thin and harder microgel shell leads to side-to-side ordering orientated parallel to the compression direction. In addition, the thin and harder microgel shell induces clustering of the microgels in the dilute state, indicating the presence of strong capillary interactions. Our findings highlight the relevance of softness for the complex ordering of anisotropic hybrid microgels at interfaces.

Modeling the assembly of oppositely charged multi-indented lock- and key-colloids.

The interactions between oppositely charged multi-indented lock- and spherical key-particles are investigated by means of Monte Carlo simulations at low volume fractions. The specificity of the interactions is initially investigated in an excess of either lock- or key-particles, and we find ordered clusters with highly directional bonds. This suggests electrostatics alone to be capable of inducing the assembly of specifically bound clusters. Considering different numbers of indentations and number ratios corresponding to perfect lattices (cubic/hexagonal/diamond), we however only find gel-like structures with no tendency to form dense ordered aggregates or lattices. We conjecture that the high entropic cost that comes with specific binding of several keys to a single lock impedes the spontaneous formation of defined lattices at low volume fractions and "lock" the assembly into disordered gel-like structures.

Assembling responsive microgels at responsive lipid membranes.

Directed colloidal self-assembly at fluid interfaces can have a large impact in the fields of nanotechnology, materials, and biomedical sciences. The ability to control interfacial self-assembly relies on the fine interplay between bulk and surface interactions. Here, we investigate the interfacial assembly of thermoresponsive microgels and lipogels at the surface of giant unilamellar vesicles (GUVs) consisting of phospholipids bilayers with different compositions. By altering the properties of the lipid membrane and the microgel particles, it is possible to control the adsorption/desorption processes as well as the organization and dynamics of the colloids at the vesicle surface. No translocation of the microgels and lipogels through the membrane was observed for any of the membrane compositions and temperatures investigated. The lipid membranes with fluid chains provide highly dynamic interfaces that can host and mediate long-range ordering into 2D hexagonal crystals. This is in clear contrast to the conditions when the membranes are composed of lipids with solid chains, where there is no crystalline arrangement, and most of the particles desorb from the membrane. Likewise, we show that in segregated membranes, the soft microgel colloids form closely packed 2D crystals on the fluid bilayer domains, while hardly any particles adhere to the more solid bilayer domains. These findings thus present an approach for selective and controlled colloidal assembly at lipid membranes, opening routes toward the development of tunable soft materials.

Influence of Size and Cross-Linking Density of Microgels on Cellular Uptake and Uptake Kinetics.

The unique pH and temperature responsiveness of PNIPAM-based microgels make them a promising target for novel biomedical applications such as cellular drug delivery systems. However, we lack a comprehensive understanding of how the physicochemical properties of microgels relate to their interaction with cells. Here, we show that HEK293T cells take up PNIPAM-based microgels on a second-to-minute time scale. Uptake rates are determined by microgel size and cross-linker content. Using fluorescence confocal live-cell microscopy, we observe microgel uptake in real time and describe cellular uptake kinetics. Experiments reveal that small and less cross-linked microgels show faster uptake kinetics than microgels of larger size or higher cross-linker content. Only microgels that are larger than 800 nm in diameter and have cross-linking contents of 10-15 mol % do not show translocation into cells. Together, these results provide insight into microgel-cell interactions and generate quantitative information on the deterministic role of microgel architecture-i.e., size and rigidity-for uptake by a prototypical human cell line.

A microgel-Pickering emulsion route to colloidal molecules with temperature-tunable interaction sites.

A simple Pickering emulsion route has been developed for the assembly of temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) microgel particles into colloidal molecules comprising a small number of discrete microgel interaction sites on a central oil emulsion droplet. Here, the surface activity of the microgels serves to drive their assembly through adsorption to growing polydimethylsiloxane (PDMS) emulsion oil droplets of high monodispersity, prepared in situ via ammonia-catalysed hydrolysis and condensation of dimethyldiethoxysilane (DMDES). A dialysis step is employed in order to limit further growth once the target assembly size has been reached, thus yielding narrowly size-distributed, colloidal molecule-like microgel-Pickering emulsion oil droplets with well-defined microgel interaction sites. The temperature-responsiveness of the PNIPAM interaction sites will allow for the directional interactions to be tuned in a facile manner with temperature, all the way from soft repulsive to short-range attractive as the their volume phase transition temperature (VPTT) is crossed. Finally, the microgel-Pickering emulsion approach is extended to a mixture of PNIPAM and poly(N-isopropylmethacrylamide) (PNIPMAM) microgels that differ with respect to their VPTT, this in order to prepare patchy colloidal molecules where the directional interactions will be more readily resolved.

Flow properties reveal the particle-to-polymer transition of ultra-low crosslinked microgels.

Exploiting soft, adaptive microgels as building blocks for soft materials with controlled and predictable viscoelastic properties is of great interest for both industry and fundamental research. Here the flow properties of different poly(N-isopropylacrylamide) (pNIPAM) microgels are compared: regularly crosslinked versus ultra-low crosslinked (ULC) microgels. The latter are the softest microgels that can be produced via precipitation polymerization. The viscosity of ULC microgel suspensions at low concentrations can be described with models typically used for hard spheres and regularly crosslinked microgels. In contrast, at higher concentrations, ULC microgels show a much softer behavior compared to regularly crosslinked microgels. The increase of the storage modulus with concentration discloses that while for regularly crosslinked microgels the flow properties are mainly determined by the more crosslinked core, for ULC microgels the brush-like interaction is dominant at high packing fractions. Both the flow curves and the increase of the storage modulus with concentration indicates that ULC microgels can form glass and even reach an apparent jammed state despite their extreme softness. In contrast, the analysis of oscillatory frequency sweep measurements show that when approaching the glass transition the ultra-low crosslinked microgels behave as the regularly crosslinked microgels. This is consistent with a recent study showing that in this concentration range the equilibrium phase behavior of these ULC microgels is the one expected for regularly crosslinked microgels.

Modeling the assembly of oppositely charged lock- and key-colloids.

The interaction of oppositely charged lock- and key-colloids is investigated using computer simulations. We show that indented spheres, i.e., lock-particles, can be specifically assembled with spherical key-particles using solely electrostatic interactions in addition to a hard overlap potential. An analytic description of the entropic and energetic contributions is derived and supported by simulations and explicit energy calculations, respectively. The analytic expression of the electrostatic contribution is further employed to build up a schematic model allowing for efficient large-scale Monte Carlo simulations. The influence of the charge/ionic strength, the degree of indentation, and the size/number ratio is discussed by analyzing the specific and unspecific associations from the simulations. Herein, both particle design and mixing conditions lead to the formation of stable specific clusters analogous to colloidal molecules whose valence is defined by the number of lock-particles associated with a key-particle. In addition, the approach is extended to the encapsulation of an excess of small key-particles in largely indented lock-particles. These two examples exemplify that highly specific pairwise interactions can be implemented by using solely oppositely charged particles with complementary geometries, which opens the road for a rational design of complex hierarchical self-assemblies of complementary building blocks.

Phase Behavior of Bowl-Shaped Colloids: Order and Dynamics in Plastic Crystals and Glasses.

Charged fluorescent bowl-shaped colloids consisting of a polystyrene core surrounded by a poly(N-isopropylmethacrylamide) shell are obtained by nanoengineering spherical composite microgels. The phase diagram of these soft bowl-shaped colloids interacting through long-range Yukawa-type interactions is investigated using confocal laser scanning microscopy. The bowl-shaped structure leads to marked differences in phase-behavior compared to their spherical counterpart. With increasing number density, a transition from a fluid to a plastic crystal phase, with freely rotating particles, followed by a glass-like state is observed. It is found that the anisotropic bowl shape frustrates crystallization and slows down crystallization kinetics and causes the glass-like transition to shift to a significantly lower volume fraction than for the spheres. Quantitative analysis of the positional and orientational order demonstrates that the plastic crystal phase exhibits quasi-long range translational order and orientational disorder, while in the disordered glass-like phase the long-range translational order vanishes and short-range rotational order appears, dictated by the specific bowl shape. It is further shown that the different structural transitions are characterized by decoupling of the translational and orientational dynamics.

Directed Self-Assembly of Polarizable Ellipsoids in an External Electric Field.

The interplay between shape anisotropy and directed long-range interactions enables the self-assembly of complex colloidal structures. As a recent highlight, ellipsoidal particles polarized in an external electric field were observed to associate into well-defined tubular structures. In this study, we systematically investigate such directed self-assembly using Monte Carlo simulations of a two-point-charge model of polarizable prolate ellipsoids. In spite of its simplicity and computational efficiency, we demonstrate that the model is capable of capturing the complex structures observed in experiments on ellipsoidal colloids at low volume fractions. We show that, at sufficiently high electric field strength, the anisotropy in shape and electrostatic interactions causes a transition from three-dimensional crystal structures observed at low aspect ratios to two-dimensional sheets and tubes at higher aspect ratios. Our work thus illustrates the rich self-assembly behavior accessible when exploiting the interplay between competing long- and short-range anisotropic interactions in colloidal systems.

Colloidal assembly and 3D shaping by dielectrophoretic confinement.

For decades, scientists and engineers have strived to design means of assembling colloids into ordered structures. By now, the literature is quite peppered with reports of colloidal assemblies. However, the available methods can assemble only a narrow range of structures or are applicable to specific types of colloids. There are still only few generic methods that would lead to arbitrary colloidal arrays or would shape colloidal assemblies into predesigned structures. Here, we first discuss in detail how to spatially control the assembly and crystallization of colloids through the balance of dielectrophoretic and dipolar forces. Furthermore, we demonstrate how to flexibly program and shape arrays of 3D microstructures that can be permanently affixed by in situ UV polymerization and calcination by using two facing similar or distinct micro-fabricated electrodes.

Multiscale directed self-assembly of composite microgels in complex electric fields.

This study explored the application of localized electric fields for reversible directed self-assembly of colloidal particles in 3 dimensions. Electric field microgradients, arising from the use of micro-patterned electrodes, were utilized to direct the localization and self-assembly of polarizable (charged) particles resulting from a combination of dielectrophoretic and multipolar forces. Deionized dispersions of spherical and ellipsoidal core-shell microgels were employed for investigating their assembly under an external alternating electric field. We demonstrated that the frequency of the field allowed for an exquisite control over the localization of the particles and their self-assembled structures near the electrodes. We extended this approach to concentrated binary dispersions consisting of polarizable and less polarizable composite microgels. Furthermore, we utilized the thermosensitivity of the microgels to adjust the effective volume fraction and the dynamics of the system, which provided the possibility to dynamically "solidify" the assembly of the field-responsive particles by a temperature quench from their initial fluid state into an arrested crystalline state. Reversible solidification enables us to re-write/reconstruct various 3 dimensional assemblies by varying the applied field frequency.

Anisotropic magnetic particles in a magnetic field.

We characterize the structural properties of magnetic ellipsoidal hematite colloids with an aspect ratio ρ ≈ 2.3 using a combination of small-angle X-ray scattering and computer simulations. The evolution of the phase diagram with packing fraction ϕ and the strength of an applied magnetic field B is described, and the coupling between orientational order of magnetic ellipsoids and the bulk magnetic behavior of their suspension addressed. We establish quantitative structural criteria for the different phase and arrest transitions and map distinct isotropic, polarized non-nematic, and nematic phases over an extended range in the ϕ-B coordinates. We show that upon a rotational arrest of the ellipsoids around ϕ = 0.59, the bulk magnetic behavior of their suspension switches from superparamagnetic to ordered weakly ferromagnetic. If densely packed and arrested, these magnetic particles thus provide persisting remanent magnetization of the suspension. By exploring structural and magnetic properties together, we extend the often used colloid-atom analogy to the case of magnetic spins.

Effective interactions between soft-repulsive colloids: experiments, theory, and simulations.

We describe a combined experimental, theoretical, and simulation study of the structural correlations between cross-linked highly monodisperse and swollen Poly(N-isopropylacrylamide) microgel dispersions in the fluid phase in order to obtain the effective pair-interaction potential between the microgels. The density-dependent experimental pair distribution functions g(r)'s are deduced from real space studies using fluorescent confocal microscopy and compared with integral equation theory and molecular dynamics computer simulations. We use a model of Hertzian spheres that is capable to well reproduce the experimental pair distribution functions throughout the fluid phase, having fixed the particle size and the repulsive strength. Theoretically, a monodisperse system is considered whose properties are calculated within the Rogers-Young closure relation, while in the simulations the role of polydispersity is taken into account. We also discuss the various effects arising from the finite resolution of the microscope and from the noise coming from the fast Brownian motion of the particles at low densities, and compare the information content from data taken in 2D and 3D through a comparison with the corresponding simulations. Finally different potential shapes, recently adopted in studies of microgels, are also taken into account to assess which ones could also be used to describe the structure of the microgel fluid.

Nonionic Microgels Adapt to Ionic Guest Molecules: Superchaotropic Nanoions.

Microgels are commonly applied as solute carriers, where the size, density, and functionality of the microgels depend on solute binding. As representatives for ionic solutes with high affinity for the microgel, we study here the effect of superchaotropic Keggin polyoxometalates (POMs) PW12O403- (PW) and SiW12O404- (SiW) on the aqueous swelling and internal structure of nonionic poly(N-isopropylacrylamide) (pNiPAM) microgels by light scattering techniques and small-angle X-ray scattering. Due to their weak hydration, these POMs bind spontaneously to the microgels at millimolar concentrations. The microgels thus become charged and swell at low POM concentration, surprisingly without strongly increasing the volume phase transition temperature, and deswell at higher POM concentration. The swelling arises because of the osmotic pressure of dissociated counterions of the POMs, while the deswelling is due to POMs acting as physical cross-links in the microgels under screened electrostatics in NaCl or excess POM solution. This swelling/deswelling transition is sharper for PW than for SiW related to the lower charge density, weaker hydration, and stronger binding of PW. The POMs elicit qualitatively and quantitatively different swelling effects from ionic surfactants and classical salts. Moreover, the network softness and topology govern the swelling response upon POM binding. The softer the microgel, the stronger is the swelling response, while, inside the microgel, regions of high polymer density swell/contract more upon electric charging/cross-linking than regions with low polymer density. POM binding thus enables fine-tuning of microgel properties and highlights the role of network topology in microgel swelling. Because POMs decompose at an alkaline pH, these POM/microgel systems also exhibit pH-responsive swelling in addition to the typical temperature responsiveness of pNiPAM microgels.