Stiffness tomography of ultra‐soft nanogels by atomic force microscopyUrheberrecht: © F. Schulte
M. F. Schulte, S. Bochenek, M. Brugnoni, A. Scotti, A. Mourran, and W. Richtering
Angew. Chem. Int. Ed. 2020, DOI: 10.1002/anie.202011615
The softness of nanohydrogels results in unique properties and recently attracted tremendous interest due to the multi‐functionalization of interfaces. For all these applications, the nanogels’ structure is of great importance but was not investigable on a nanometric scale before. In this article, we study extremely soft temperature‐sensitive ultra‐low cross‐linked (ULC) nanogels adsorbed to the solid/water interface by atomic force microscopy (AFM). Their extreme softness hampers the imaging: the ULC nanogels are “invisible” in the classical 2D height image since a sharp tip fully penetrates these porous networks with very low forces in the range of steric interactions (ca. 100 pN). Nonetheless, the detailed evaluation of Force Volume data allows us to resolve their overall shape and at the same time their internal structure with nanometric and piconewton resolution in all three dimensions. The nanogels exhibit an extraordinary disk‐like and entirely homogeneous but extremely soft structure – even softer than polymer brushes. Moreover, the temperature‐sensitive nanogels can be switched on demand between the ultra‐soft and a very stiff state.
Effect of the 3D Swelling of Microgels on Their 2D Phase Behavior at the Liquid–Liquid InterfaceUrheberrecht: © S. Bochenek
Bochenek, S.; Scotti, A.; Ogieglo, W.; Fernandez-Rodriguez, M.-A.; Schulte, M. F.; Gumerov, R. A.; Bushuev, N. V.; Potemkin, I. I.; Wessling, M.; Isa, L.; Richtering, W.; Langmuir 2019, 35 (51), 16780–16792.
We investigate soft, temperature-sensitive microgels at fluid interfaces. Though having an isotropic, spherical shape in bulk solution, the microgels become anisotropic upon adsorption. The structure of microgels at interfaces is described by a core–corona morphology. Here, we investigate how changing temperature across the microgel volume phase transition temperature, which leads to swelling/deswelling of the microgels in the aqueous phase, affects the phase behavior within the monolayer. We combine compression isotherms, atomic force microscopy imaging, multiwavelength ellipsometry, and computer simulations. At low compression, the interaction between adsorbed microgels is dominated by their highly stretched corona and the phase behavior of the microgel monolayers is the same. The polymer segments within the interface lose their temperature-sensitivity because of the strong adsorption to the interface. At high compression, however, the portions of the microgels that are located in the aqueous side of the interface become relevant and prevail in the microgel interactions. These portions are able to collapse and, consequently, the isostructural phase transition is altered. Thus, the temperature-dependent swelling perpendicular to the interface (“3D”) affects the compressibility parallel to the interface (“2D”). Our results highlight the distinctly different behavior of soft, stimuli-sensitive microgels as compared to rigid nanoparticles.
Influence of Size and Cross-Linking Density of Microgels on Cellular Uptake and Uptake KineticsUrheberrecht: © Victoria K. Switacz
Victoria K. Switacz, Sarah K. Wypysek, Rudolf Degen, Jérôme J. Crassous, Marc Spehr, and Walter Richtering
Biomacromolecules 2020 , 21, 11, 4532-4544.
In this work, we investigate the interactions of various PNIPAM-based microgels with HEK293T cells to gain a more comprehensive understanding of the relation of the physico -chemical properties of microgels to their interactions with cells. Using fluorescence confocal live-cell microscopy, we observe microgel uptake in real-time and describe cellular uptake kinetics . We show that HEK293T cells take up PNIPAM-based microgels on a second-to-minute time scale. A combination of microgel size and cross-linker content determines their uptake rates. We reveal that s mall and less cross-linked microgels show faster uptake kinetics than microgels of larger size or higher cross-linking 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.
These results provide valuable information towards a conceptual understanding of microgel–cell interactions that will allow a more custom design of microgel architectures for specific biomedical applications with increased precision, reliability, and efficiency.
Screening lengths and osmotic compressibility of flexible polyelectrolytes in excess salt solutions
Carlos G. Lopez, Ferenc Horkay, Matan Mussel, Ronald L. Jones and Walter Richtering, Soft Matter, 2020 Advance Article
We report results of small angle neutron scattering measurements made on sodium polystyrene sulfonate in aqueous salt solutions. The correlation length (ξ) and osmotic compressibility are measured as a function of polymer (c) and added salt (c S) concentrations, and the results are compared with scaling predictions and the random-phase approximation (RPA). In Dobrynin et al.'s scaling model the osmotic pressure consists of a counter-ion contribution and a polymer contribution. The polymer contribution is found to be two orders of magnitude smaller than expected from the scaling model, in agreement with earlier observations made on neutral polymers in good solvent condition. RPA allows the determination of single-chain dimensions in semidilute solutions at high polymer and added salt concentrations, but fails for c S ≤ 2 M. The χ parameter can be modelled as the sum of an intrinsic contribution (χ 0) and an electrostatic term: χ ∼ χ 0 + K′/√c S, where χ 0 > 0.5 is consistent with the hydrophobic nature of the backbone of NaPSS. The dependence of χ elec ∼ 1/√c S disagrees with the random-phase approximation (χ elec ∼ 1/c s), but agrees with the light scattering results in dilute solution and Dobrynin et al.'s scaling treatment of electrostatic excluded volume.
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Tailoring the Cavity of Hollow Polyelectrolyte MicrogelsUrheberrecht: © S. Wypysek
In this study, we demonstrate how the size and structure of the cavity of hollow charged microgels may be controlled by varying pH and ionic strength. Hollow charged microgels based on N ‐ isopropylacrylamide with ionizable co‐monomers ( itaconic acid) combine advanced structure with enhanced responsiveness to external stimuli. Structural advantages accrue from the increased surface area provided by the extra internal surface. Extreme sensitivity to pH and ionic strength due to ionizable moieties in the polymer network differentiates these soft colloidal particles from their uncharged counterparts, which sustain a hollow structure only at cross‐link densities sufficiently high that stimuli sensitivity is reduced. Using small‐angle neutron and light scattering, increased swelling of the network in the charged state accompanied by an expanded internal cavity is observed. Upon addition of salt, the external fuzziness of the microgel surface diminishes while the internal fuzziness grows. These structural changes are interpreted via Poisson–Boltzmann theory in the cell model.
Wypysek, S. K., Scotti, A., Alziyadi , M. O., Potemkin, I. I., Denton, A. R., Richtering, W., Macromol . Rapid Commun . 2020 , 41, 1900422.
Enrichment of methanol inside pNIPAM gels in the cononsolvency-induced collapseUrheberrecht: © K. Nothdurft
In this work, we studied poly-N-isopropylacrylamide (pNIPAM) gels by spatially resolved Raman microspectroscopy in various water-methanol mixtures to gain new insights on the cononsolvency effect. Cononsolvency describes the phenomenon that certain mixtures of two good solvents (e.g. water and methanol) cause a unique transition from a flexible, swollen macromolecular network to a collapsed particle. So far, the mechanisms underlying cononsolvency have not been fully elucidated. Mass balancing in combination with spectral modelling of the Raman measurements, allowed the calculation of the solvent composition inside the pNIPAM gel. The results show an increased methanol fraction inside the collapsed gel as compared to its surroundings. Furthermore, the sensitivity of the vibrational bands of methanol to its local hydrogen bonding environment allow to derive information about the molecular interactions. The methanol peak shifts measured inside the gel point towards donor-type hydrogen bonds between methanol and the peptide group of pNIPAM in the cononsolvency-induced collapse.
K. Nothdurft, D. H. Müller, T. Brands, A. Bardow, W. Richtering, Phys. Chem. Chem. Phys., 2019, 21, 22811-22818. (PCCP Editor’s choice + PCCP HOT Article 2019)
Anisotropic Hollow Microgels That Can Adapt Their Size, Shape, and SoftnessUrheberrecht: © Anne Nickel
A. C. Nickel, A. Scotti, J. E. Houston, T. Ito, J. Crassous, J. S. Pedersen, W. Richtering, Nano Lett. 2019, 19, 11, 8161-8170, DOI: 10.1021/acs.nanolett.9b03507
This work addresses the challenge of creating hollow and anisotropically shaped thermoresponsive microgels. Sacrificial elliptical hematite silica particles are utilized as a template for the synthesis of a cross-linked N-isopropylacrylamide (NIPAm) shell. By varying the amount of NIPAm, two anisotropic microgels were synthesized with either a thin or thick microgel shell. These precursor core–shell and the resulting hollow microgels were characterized using a combination of light, X-ray, and neutron scattering. New form factor models have been developed for fitting the scattering data. With such models, we demonstrated the existence of the cavity and simultaneously the anisotropic character of the microgels. Furthermore, we show that the thickness of the shell has a major influence on the shape and the cavity dimension of the microgel after etching of the sacrificial core. Finally, the effect of temperature is investigated, showing that changes in size, softness, and aspect ratio are triggered by temperature.————————————————————————————————————————————————————
Nanogels and Microgels in Fundamental and Applied Sciences
Exploring the colloid-to-polymer transition for ultra-low crosslinked microgels from three to two dimensions
In this work we study ultra-low crosslinked poly(N-isopropylacrylamide) microgels (ULC), which can behave like colloids or flexible polymers depending on their environment, e.g. dimensionality, compression or other external stimuli. Small-angle neutron scattering shows that the structure of the ULC microgels in bulk aqueous solution is characterized by a density profile that decays smoothly from the center to a fuzzy surface. Their phase behavior and rheological properties are those of colloids interacting with a soft potential. However, when these microgels are confined at an oil-water interface, their behavior resembles that of flexible macromolecules. Once monolayers of ultra-low crosslinked microgels are compressed, deposited on solid substrate and studied with atomic-force microscopy, a concentration-dependent topography is observed. Depending on the compression, these microgels can behave as flexible polymers, covering the substrate with a uniform film, or as colloidal microgels leading to a monolayer of particles.
A. Scotti, S. Bochenek, M. Brugnoni, M. A. Fernandez-Rodriguez, M. F. Schulte, J. E. Houston, A. P. H. Gelissen, I. I. Potemkin, L. Isa, and W. Richtering
Nature Communications 10, 1418 (2019).
nature COMMUNICATIONS, Editors' Highlights
Urheberrecht: © Monia Brugnoni
How do microgels collapse?Urheberrecht: © Walter Richtering
Time-resolved structural evolution during the collapse of responsive hydrogels: The microgel-to-particle transition
R. Keidel, A. Ghavami, D.M. Lugo, G. Lotze, O. Virtanen, P. Beumers, J.S. Pedersen, A. Bardow, R.G. Winkler and W. Richtering
Science Advances 06 Apr 2018:
Vol. 4, no. 4, eaao7086
The structural adaption of microgels to the environment involves a unique transition from a flexible, swollen finite-size macromolecular network, characterized by a fuzzy surface, to a colloidal particle with homogeneous density and a sharp surface. In this contribution, we determine, for the first time, the structural evolution during the microgel-to-particle transition. Time-resolved small-angle x-ray scattering experiments and computer simulations unambiguously reveal a two-stage process: In a first, very fast process, collapsed clusters form at the periphery, leading to an intermediate, hollowish core-shell structure that slowly transforms to a globule. This structural evolution is independent of the type of stimulus and thus applies to instantaneous transitions as in a temperature jump or to slower stimuli that rely on the uptake of active molecules from and/or exchange with the environment. The fast transitions of size and shape provide unique opportunities for various applications as, for example, in uptake and release, catalysis, or sensing.
Hollow microgels squeezed in overcrowded environmentsUrheberrecht: © Walter Richtering
A. Scotti, M. Brugnoni, A. A. Rudov, J. E. Houston, I. I. Potemkin, and W. Richtering
The Journal of Chemical Physics
148, 174903 (2018)
We study how a cavity changes the response of hollow microgels with respect to regular ones in
overcrowded environments. The structural changes of hollowpoly(N-isopropylacrylamide) microgels
embedded within a matrix of regular ones are probed by small-angle neutron scattering with contrast
variation. The form factors of the microgels at increasing compressions are directly measured. The
decrease of the cavity size with increasing concentration shows that the hollow microgels have an
alternative way with respect to regular cross-linked ones to respond to the squeezing due to their
neighbors. The structural changes under compression are supported by the radial density profiles
obtained with computer simulations. The presence of the cavity offers to the polymer network the
possibility to expand toward the center of the microgels in response to the overcrowded environment.
Furthermore, upon increasing compression, a two step transition occurs: First the microgels are
compressed but the internal structure is unchanged; then, further compression causes the fuzzy shell
to collapse completely and reduce the size of the cavity. Computer simulations also allow studying
higher compression degrees than in the experiments leading to the microgel’s faceting.
Anionic shell shields a cationic core allowing for uptake and release of polyelectrolytes within core-shell responsive microgelsUrheberrecht: © A. Gelissen
Arjan P. H. Gelissen, Andrea Scotti, Sarah K. Turnhoff, Corinna Janssen, Aurel Radulescu, Andrij Pich, Andrey A. Rudov, Igor I. Potemkin and Walter Richtering , Soft Matter , 2018, Advance Article,
To realize carriers for drug delivery, cationic containers are required for anionic guests. Nevertheless, the toxicity of cationic carriers limits their practical use. In this study, we investigate a model system of polyampholyte N-isopropylacrylamide (NIPAM)-based microgels with a cationic core and an anionic shell to study whether the presence of a negative shell allows shielding the cationic core while still enabling the uptake and release of the anionic guest polyelectrolytes. These microgels are loaded with polystyrene sulfonate of different molecular weights. By means of small-angle neutron scattering, we evaluate the spatial distribution of polystyrene sulfonate within the microgels. The guest molecules are located in different parts of the core-shell microgels depending on their size. By combining these scattering results with UV-Vis and electrophoretic mobility we gain complementary results to investigate the uptake and release process of polyelectrolytes in polyampholyte core-shell microgels. Moreover, Brownian molecular dynamic simulations are performed to compare experimental and theoretical results of this model. Our findings demonstrate that the presence of a shell still enables efficient uptake into the cationic core of guest molecules. These anionic guest molecules can be released through an anionic shell. Furthermore, the presence of a shell enhances the stability of the microgel-polyelectrolyte complexes with respect to the cationic precursor microgel alone.
Probing the Internal Heterogeneity of Responsive Microgels Adsorbed to an Interface by a Sharp SFM Tip: Comparing Core-Shell and Hollow MicrogelsUrheberrecht: © M. F. Schulte
M. F. Schulte, A. Scotti, A. P. H. Gelissen, W. Richtering, A. Mourran, Langmuir 2018 (accepted).
Silica core – PNIPAM shell and corresponding hollow microgels were studied by scanning force microscopy (SFM). We show that swollen microgels are penetrated strongly by a sharp SFM tip. The force profile during insertion of the tip into the polymer network enables to determine a depth-dependent contact resistance which closely correlates with the density profiles determined in solution by small-angle neutron scattering (SANS). Remarkably, while currently used techniques only generate an average of the z-profile, SFM provides spatially resolved internal structure information of individual microgels. We found that the cavity of the swollen hollow microgels is still present when adsorbed to the solid substrate.
Swelling of a Responsive Network within Different Constraints in Multi-Thermosensitive MicrogelsUrheberrecht: © M. Brugnoni
M. Brugnoni, A. Scotti, A. A. Rudov, A. P. H. Gelissen, T. Caumanns, A. Radulescu, T. Eckert, A. Pich, I. I. Potemkin, W. Richtering, 2018, Macromolecules, DOI: 10.1021/acs.macromol.7b02722.
Silica-core double-shell and hollow double-shell microgels made of an inner poly(N-isopropylmethacrylamide) and an outer poly(N-isopropylacrylamide) shell are studied by exploiting the distinct temperature sensitivities of the polymers. The swelling states of the two shells can be tuned by temperature changes enabling three different swelling states: above, below, and between the distinct volume phase transition temperatures of the two polymers. This enables to investigate the effect of different constraints on the swelling of the inner network. Small-angle neutron scattering with contrast variation discloses how the expansion of the inner shell strongly depends on the material and swelling state of its constraints. In the presence of the stiff core, the microgels show a considerable interpenetration of the polymeric shells: the inner network expands into the outer deswollen shell. This interpenetration vanishes when the outer network is swollen. Furthermore, as predicted by our computer simulations, an appropriate choice of cross-linking density enables the generation of hollow double-shell nanocapsules. Finally, the inner shell undergoes a push−pull effect. At high temperature, the collapsed outer shell pushes the swollen inner network into the cavity. At lower temperature, the swelling of the outer network contrary pulls the inner shell back toward the external periphery.