Understanding the internal architecture of copolymer microgels is crucial for establishing how nanoscale polymer organization controls their stimuli-responsive behavior. Here we focus on thermoresponsive P(N-isopropylacrylamide-co-N-isopropyl-methacrylamide), P(NIPAM-co-NIPMAM), microgels with varying mole fraction of the components, synthesized via radical precipitation polymerization, and we demonstrate that changes in their volume phase transition and equilibrium swelling are governed by composition-dependent internal heterogeneity. Comparison between small-angle neutron scattering (SANS) with isotopic labeling and monomer-resolved simulations show a block-like monomer distribution of the two components. SANS analysis reveals a universal maximum in the polymer mesh correlation length near the transition, evidencing coexistence of collapsed NIPAM-rich and swollen domains. The correlation length increases with increasing NIPMAM content, with a maximum for 75 mol % NIPMAM, implying sparse collapsed regions within the network and thus a large degree of heterogeneity induced by the presence of an increasingly large fraction of intercalated, non-collapsing PNIPMAM. The maximum heterogeneity correlates with the equilibrium swelling ratio, indicating that collapsed microgels retain a structural memory of the transition and present a less-compliant structure in response to temperature variations. Overall, these insights highlight a complex effect of the block-like monomer distribution on the responsive properties of copolymer microgels with different compositions, thus providing a design rule for tailoring responsive colloids for functional soft materials.

The internal architecture of poly(N-isopropylacrylamide) (PNIPAM) microgels, which switches from fuzzy-sphere to star-like when the standard N,N'-methylenebis(acrylamide) (BIS) crosslinker is replaced with ethylene glycol dimethacrylate (EGDMA), critically determines their interactions and swelling behavior. Here, we systematically investigate the role of the surfactant and crosslinker content in modulating the internal structure of the microgels using Dynamic Light Scattering, Small-angle X-ray Scattering and monomer-resolved numerical simulations. We reveal that the presence of the surfactant is crucial for obtaining the star-like architecture, and that the transition from the star-like regime to a more core-dominated structure occurs above a threshold EGDMA concentration. Monomer-resolved simulations capture how the role of surfactant differs between EGDMA-crosslinked and BIS-crosslinked microgels. Our findings establish a direct synthesis-structure relationship, providing a clear guidance for the rational design of soft, star-like microgels with ultra-soft interactions, strenghtening the connection between microgels and model star polymers.

Plasmonic nanoparticles (NPs) integrated within thermoresponsive polymeric microgels provide a versatile platform for the realization of stimuli-responsive optical materials, where the microgel volume phase transition enables dynamic control of plasmon coupling. This study uncovers a counter-intuitive re-entrant behavior with increasing NP loading in which plasmon coupling initially strengthens and subsequently weakens beyond a critical NP-to-microgel number ratio. By combining light and X-ray scattering techniques with optical spectroscopy and electrophoretic mobility measurements, it is demonstrated that plasmon coupling is governed not only by the interparticle distance between NPs confined within individual microgels, but also by the colloidal stability of the hybrid complexes. At intermediate NP loadings, surface charge inhomogeneities induced by NP adsorption promote aggregation of microgel-NPs complexes, resulting in enhanced plasmon coupling. In contrast, when the complexes remain colloidally stable, coupling is dictated solely by NP organization within the corona of individual microgels. A quantitative relationship between plasmon coupling and interparticle distance reveals two distinct coupling regimes. This behavior is rationalized through a phase diagram linking colloidal stability to optical response. These findings identify colloidal stability as a key parameter for designing soft plasmonic systems with programmable optical properties.

Abstract The internal architecture of poly(N-isopropylacrylamide) (PNIPAM) microgels, which switches from fuzzy-sphere to star-like structures when the standard N,N′-methylenebis(acrylamide) (BIS) cross-linker is replaced with ethylene glycol dimethacrylate (EGDMA), critically determines their interactions and swelling behavior. Here, we systematically investigate the role of the surfactant and cross-linker content in modulating the internal structure of the microgels using dynamic light scattering, small-angle X-ray scattering, and monomer-resolved numerical simulations. We reveal that the presence of the surfactant is crucial for obtaining the star-like architecture, and that the transition from the star-like regime to a more core-dominated structure occurs above a threshold EGDMA concentration. Monomer-resolved simulations capture how the role of surfactant differs between EGDMA-cross-linked and BIS-cross-linked microgels. Our findings establish a direct synthesis–structure relationship, providing a clear guidance for the rational design of soft, star-like microgels with ultrasoft interactions, strengthening the connection between microgels and model star polymers.

Star-like microgels have recently emerged as a promising class of thermoresponsive soft colloids that have an internal architecture similar to that of star polymers. Here, we perform extensive monomer-resolved simulations to theoretically establish this analogy. First, we characterize the effective potential between star-like microgels, finding that it is Gaussian for an extended range of distances, in stark contrast to the Hertzian-like potential of standard microgels, but almost identical to that of star polymers with a core partially covered by chains. Next, we investigate the ratio between gyration and hydrodynamic radii across the volume-phase transition, showing qualitative agreement with both star polymers and experimental data. Finally, we estimate the bulk modulus, finding star-like microgels significantly softer than standard microgels and comparable to star polymers. The present work thus demonstrates that star-like microgels behave as ultrasoft particles, akin to star polymers, paving the way for their exploration at high concentrations.

The complexation of plasmonic nanoparticles (NPs) and thermoresponsive microgels is widely recognized as a powerful route to realize hybrid systems with tunable optical properties for different applications. At the same time, it provides a unique experimental platform to investigate the physics of NP organization on curved two-dimensional surfaces, a fundamental problem with implications spanning from biology to materials science yet unexplored at the nanoscale. However, a microscopic description of the mechanisms governing the spatial organization of the NPs and their rearrangement across the microgel volume phase transition (VPT) is lacking so far. Combining small-angle X-ray scattering and state-of-the-art simulations, we uncover how the microgel VPT controls NP-NP interactions, showing that temperature-induced microgel collapse drives a redistribution of NPs toward the periphery, with a tendency to order on the spherical surface. Moreover, we quantitatively reproduce both the structural and optical experimental data through a simple toy model, ultimately establishing for the first time a direct link between the interparticle distance and plasmon coupling. Our study paves the way for experimentally investigating phase transitions on tunable curved surfaces at the nanoscale, achieving fine control of their plasmonic response.

The inner structure of polymeric microgels critically influences their responsiveness and potential applications, yet remaining challenging to resolve at molecular resolution. In this work, a structural characterization of thermoresponsive copolymer microgels is provided by integrating small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance (NMR) measurements with multi-scale simulations. Specifically, Poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide), P(NIPAM-co-NIPMAM), copolymer microgels, in which a random monomer distribution is conventionally assumed, are considered. By synthesizing different samples, including isotopically labeled microgels via selective deuteration, the microgels swelling behavior is probed and distinct polymer-specific signatures are revealed. To elucidate their internal distribution, monomer-resolved microgel simulations are performed across different copolymer models. A direct comparison between experimental and numerical form factors provides evidence of preferential organization into block structures, challenging the prevailing view of random distribution. 13C-NMR experiments confirm NIPAM-rich blocks and atomistic simulations link this unexpected block-like architecture to distinct local hydrogen-bonding patterns. This integrated approach provides the first direct evidence of preferential block formation in P(NIPAM-co-NIPMAM) microgels. Beyond this system, these results establish a generalizable strategy for unveiling hidden structural order in copolymer microgels, offering new strategies to tailor their design and to enhance control of material responsivity.

Incorporating ionic co-monomers into polymer microgels can alter their swelling behavior and introduce pH-responsiveness; however, their effect on the internal microgel structure remains poorly understood. Here we present a comprehensive study of poly(N-isopropylacrylamide-co-acrylic acid) microgels, revealing that the incorporation of ionic groups significantly alters their internal architecture. Using dynamic and static light scattering combined with small-angle X-ray scattering, we observe pronounced differences in form factors and swelling behavior between neutral and ionic microgels. These findings can be rationalized by monomer-resolved simulations, which reproduce the experimental form factors only when charge-induced alterations to the network architecture are explicitly accounted for during in silico synthesis. Our results demonstrate that electrostatic interactions modulate not only the swelling behavior but also the internal monomer density profile, highlighting the need to integrate and extend current modeling approaches for charged microgels.

We provide experimental and numerical evidence of a new class of soft nanocolloids: star-like microgels with thermoresponsive character. This is achieved by using the standard precipitation polymerization synthesis of poly(N-isopropylacrylamide) (PNIPAM) microgels and replacing the usually employed crosslinking agent, N,N'-methylenebis(acrylamide) (BIS), with ethylene glycol dimethacrylate (EGDMA). The fast reactivity of EGDMA combined with its strong tendency to self-bind produces colloidal networks with a central, crosslinker-rich core, surrounded by a corona of long, crosslinker-free arms. These novel star-like microgels fully retain PNIPAM thermoresponsivity and undergo a volume phase transition at a temperature of 32C that is very sharp as compared to standard PNIPAM-BIS microgels, independently of crosslinker content. Dynamic light scattering and small angle X-ray scattering experiments are compared to extensive simulation results, based on ideal star polymers as well as on state-of-the-art monomer-resolved simulations, offering a microscopic evidence of the star-like internal structure of PNIPAM-EGDMA microgels. This can be described by a novel model for the form factors combining star and microgel features. The present work thus bridges the fields of star polymers and microgels, providing the former with the ability to respond to temperature via a facile synthetic route that can be routinely employed, opening the way to exploit these soft particles for a variety of fundamental studies and applicative purposes.

We provide experimental and numerical evidence of an emerging class of soft nanocolloids: star-like microgels with thermoresponsive character. This is achieved by using the standard precipitation polymerization synthesis of poly(N-isopropylacrylamide) (PNIPAM) microgels and replacing the usually employed cross-linking agent, N,N'-methylenebisacrylamide (BIS), with ethylene glycol dimethacrylate (EGDMA). The fast reactivity of EGDMA, combined with its strong tendency to self-bind, produces colloidal networks with a central, cross-linker-rich core, surrounded by a corona of long, cross-linker-free arms. These star-like microgels fully retain PNIPAM thermoresponsivity and undergo a volume phase transition at a temperature of ∼32 °C that is very sharp compared to standard PNIPAM-BIS microgels, independently of the cross-linker content. Dynamic light scattering and small-angle X-ray scattering experiments are compared to extensive simulation results, based on ideal star polymers as well as on state-of-the-art monomer-resolved simulations, offering microscopic evidence of the star-like internal structure of PNIPAM-EGDMA microgels. This can be described by an appropriate model for the form factors combining star and microgel features. The present work thus bridges the fields of star polymers and microgels, providing the former with the ability to respond to temperature via a facile synthetic route that can be routinely employed, opening the way to exploit these soft particles for a variety of fundamental studies and applicative purposes.

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration.

Data presented in the article entitled Molecular origin of the two-step mechanism of gellan aggregation.

The interplay of soft responsive particles, such as microgels, with nanoparticles (NPs) yields highly versatile complexes that show great potential for applications, ranging from plasmonic sensing to catalysis and drug delivery. However, the microgel-NP assembly process has not been investigated so far at the microscopic level, thus hindering the possibility of designing such hybrid systems a priori. In this work, we combine state-of-the-art numerical simulations with experiments to elucidate the fundamental mechanisms taking place when microgel-NP assembly is controlled by electrostatic interactions and the associated effects on the structure of the resulting complexes. We find a general behavior where, by increasing the number of interacting NPs, the microgel deswells up to a minimum size after which a plateau behavior occurs. This occurs either when NPs are mainly adsorbed to the microgel corona via the folding of the more external chains or when NPs penetrate inside the microgel, thereby inducing a collective reorganization of the polymer network. By varying microgel properties, such as fraction of cross-linkers or charge, as well as NP size and charge, we further show that the microgel deswelling curves can be rescaled onto a single master curve, for both experiments and simulations, demonstrating that the process is entirely controlled by the charge of the whole microgel-NP complex. Our results thus have a direct relevance in fundamental materials science and offer novel tools to tailor the nanofabrication of hybrid devices of technological interest.

Hypothesis: We propose significant improvements to perfluorocarbon microdroplets, conferring them colloidal stability, chemical versatility, and size control. Decafluoropentane cores are stabilized by biocompatible interfaces - either a monolayer of the cationic surfactant dimethyldioctadecylammonium bromide (DDAB) or a double shell obtained by adding crosslinked dextran methacrylate as further coating - and functionalised with gold nanoparticles. We hypothesize that this formulation enables dual, acoustic (ADV) and optical (ODV) vaporisation of microdroplets into microbubbles, yielding a versatile "phase-change " theranostic platform. Experiments: Microdroplets synthesis is optimized by high-speed homogenization methodology. Functionalisation with gold nanoparticles is achieved by electrostatic decoration. The colloidal suspension is characterised by the concerted use of dynamic light scattering, electrophoresis, and confocal microscopy, to assess microdroplets' stability. Additional structural details are provided by small-angle X-ray scattering. We analysed the ultrasound and laser-stimulated transition into microbubbles and characterised their response to ultrasound by acoustic spectroscopy.Findings: Hybrid-shelled microdroplets were produced at high density, with narrow diameter distribution (similar to 1 mu m). The highly charged surface and the long hydrocarbon tails of DDAB protruding within the core provide high stability. The elastomeric dextran layer at the water interface allows obtaining stable cavitating microbubbles by ADV exhibiting interesting viscoelastic features. The presence of gold nanoparticles unlocks the opto-thermal microdroplet vaporisation.

Optical diffraction tomography (ODT) is a label-free technique for three dimensional imaging of micron-sized objects. Coherence and limited sampling of 3D Fourier space are often responsible for the appearance of artifacts. Here we present an ODT microscope that uses low temporal coherence light and spatial light modulators to retrieve reliable 3D maps of the refractive index. A common-path interferometer, based on a spatial light modulator, measures the complex fields transmitted by a sample. Measured fields, acquired while scanning the illumination direction using a digital micro-mirror device, are fed into a Rytov reconstruction algorithm to obtain refractive index maps whose accuracy is directly evaluated on microfabricated 3D test objects. Even for challenging shapes such as pyramids, bridges, and dumbbells, we obtain volumetric reconstructions that compare very well with electron microscopy images.

Multi-responsive nanomaterials based on the self-limited assembly of plasmonic nanoparticles are of great interest due to their widespread employment in sensing applications. We present a thorough investigation of a hybrid nanomaterial based on the protein-mediated aggregation of gold nanoparticles at varying protein concentration, pH and temperature. By combining Small Angle X-ray Scattering with extinction spectroscopy, we are able to frame the morphological features of the formed fractal aggregates in a theoretical model based on patchy interactions. Based on this, we established the main factors that determine the assembly process and their strong correlation with the optical properties of the assemblies. Moreover, the calibration curves that we obtained for each parameter investigated based on the extinction spectra point out to the notable flexibility of this nanomaterial, enabling the selection of different working ranges with high sensitivity. Our study opens for the rational tuning of the morphology and the optical properties of plasmonic assemblies to design colorimetric sensors with improved performances.

The development of various degenerative diseases is suggested to be triggered by the uncontrolled organisation and aggregation of proteins into amyloid fibrils. For this reason, there are ongoing efforts to develop novel agents and approaches, including metal nanoparticle-based colloids, that dissolve amyloid structures and prevent pathogenic protein aggregation. In this contribution, the role of gold nanoparticles (AuNPs) in degrading amyloid fibrils of the model protein lysozyme is investigated. The amino acid composition of fibril surfaces before and after the incubation with AuNPs is determined at the single fibril level by exploiting the high spatial resolution and sensitivity provided by tip-enhanced and surface-enhanced Raman spectroscopies. This combined spectroscopic approach allows to reveal the molecular mechanisms driving the interaction between fibrils and AuNPs. Our results provide an important input for the understanding of amyloid fibrils and could have a potential translational impact on the development of strategies for the prevention and treatment of amyloid-related diseases.

Keratinocytes, the main cell type of the skin, are one of the most exposed cells to environmental factors, providing a first defence barrier for the host and actively participating in immune response. In fact, keratinocytes express pattern recognition receptors that interact with pathogen associated molecular patterns and damage associated molecular patterns, leading to the production of cytokines and chemokines, including interleukin (IL)-6. Herein, we investigated whether mechanical energy transported by low intensity ultrasound (US) could generate a mechanical stress able to induce the release of inflammatory cytokine such IL-6 in the human keratinocyte cell line, HaCaT. The extensive clinical application of US in both diagnosis and therapy suggests the need to better understand the related biological effects. Our results point out that US promotes the overexpression and secretion of IL-6, associated with the activation of nuclear factor-κB (NF-κB). Furthermore, we observed a reduced cell viability dependent on exposure parameters together with alterations in membrane permeability, paving the way for further investigating the molecular mechanisms related to US exposure.

We realise an antibacterial nanomaterial based on the self-limited assembly of patchy plasmonic colloids, obtained by adsorption of lysozyme to gold nanoparticles. The possibility of selecting the size of the assemblies within several hundred nanometres allows for tuning their optical response in a wide range of frequencies from visible to near infrared. We also demonstrate an aggregation-dependent modulation of the catalytic activity, which results in an enhancement of the antibacterial performances for assemblies of the proper size. The gained overall control on structure, optical properties and biological activity of such nanomaterial paves the way for the development of novel antibacterial nanozymes with promising applications in treating multi drug resistant bacteria.

The programmable assembly of DNA strands is a promising tool for building tailored bottom-up nanostructures. Here, we present a plasmonic nanosystem obtained by the base-pairing mediated aggregation of gold nanoparticles (NPs) which are separately functionalized with two different single-stranded DNA chains. Their controlled assembly is mediated by a complementary DNA "bridge" sequence. We monitor the formation of DNA assembled NP aggregates in solution, and we study their Surface Enhanced Raman Scattering (SERS) response by comparison with the single NP constituents. We interpret the revealed SERS signatures in terms of the molecular and NP organization at the nanoscale, demonstrating that the action of the DNA bridge molecule yields regular NP aggregates with controlled interparticle distance and reproducible SERS response. In perspective, this demonstrates the potential of the present system as a stable, biocompatible, and recyclable SERS sensor.