Self-Assembled Colloids

Figure 1: Isotropic and anisotropic particles with homogeneous surface, patterned surface chemistry and nanotopography.

The shape of a particle can be described by its topology (sphere, cylinder, doughnut, sheet), while the surface of a particle exhibits either homogeneous chemistry, chemical surface patterns or surface asperities, i.e. 3D topography. The behavior of particles in solution is largely determined by their interaction potential with other particles often expanding beyond distances several times larger than the particle diameter. For the recognition by interfaces or particle-particle interactions at close range, the surface structure becomes more relevant. Virus particles are probably the most prominent example from nature, where the surface structure is optimized for nanoparticle/membrane interaction facilitating internalization into cells. Viruses are the prime example for how construction from the bottom up gives access to sub-100nm particles with precise surface structure and topography. Inspired by this structuring principle, we develop self-assembly concepts for block copolymers to create nanoparticles with well-defined inner morphologies, shape, chemical surface patterns and/or topographies with few-manometer resolution.
In the following, find a list of concepts concerning the hierarchical self-assembly of ABC triblock terpolymers into multicompartment micelles, confinement-assembly of multicompartment microparticles, and the topographic patterning of nanoparticles surfaces.

Multicompartment Micelles

Figure 2. Hierarchical self-assembly route to MCMs

The hierarchical step-wise self-assembly of ABC triblock terpolymers was pioneered in our group and gave, for the first time, utmost control over size, shape, inner morphology and chemistry of multicompartment micelles. In the first work, we established the hierarchical self-assembly process involving the sequential folding of polymer blocks starting with the collapse of the B middle block in selective solvent into precursor micelles with B core and A/C corona. Although the extend of demixing of chains A and C in the corona could not be determined, we assume a certain multi-patch structure due to interplay of chain incompatibility and mixing entropy. in a subsequent step, we assemble these precursor micelles by changing the solvent conditions to be selective for only the C corona block. Since the B core remains collapsed, micelles cluster through association of the likewise insoluble A corona chains. The volume ratios of A B and C determine how many micelles cluster before enough C corona provides stabilization. This second step can be seen as supracolloidal aggregation of patchy micelles. The step-wise self-assembly eases structural reorganization and thereby allows to produce multicompartment micelles with very high uniformity. Statistical evaluation of some samples gave about 96 % trimer micelles with trigonal planar arrangement, with the remaining micelles consisting either of 4 or 2 precursor micelles (patches). We demonstrated that this principle can be applied to a range of different block chemistries, and block fractions thereby tuning the cluster size (patch number). We further found a structural transformation from spherical clusters to linear growth of precursor micelles when a critical volume fraction of core blocks was reached (VB/VA<1). Precursor micelles then form extended linear core-compartmentalized cylinder micelles with strictly alternating compartments A/B.
We have, in a very recent work, transferred these concepts to supracolloidal aggregation in water. We therefore synthesized water-soluble terpolymers of polyethylene oxide-b-polystyrene-b-poly(2vinylpyridine) and followed the hierarchical self-assembly protocol (first isopropanol then water). In isopropanol, the terpolymers formed patchy micelles with PS core and PEO/P2VP corona that further underwent supracolloidal growth of linear chains in basic water (P2VP insoluble at pH > 4).  The linear chains showed remarkable low degree of branching, i.e., precursor micelles showed high selectivity for linear growth as programmed by the terpolymer block length. 

Figure 3. Library of MCMs with controlled shape and inner morphology

In follow-up works, we demonstrated that the length of the stabilizing corona can be tailored to control the overall shape of the multicompartment micelles, whereas the volume ratio VB/VA determines the morphology inside the core in a process reminding on microphase separation in bulk. By synthesizing a range of terpolymers with identical length of the core blocks, we showed that with controlled length of the C corona block we could target e.g. micelle  spheres, cylinders, bilayer sheets and vesicles, all with a sphere morphology in the core (B spheres in A matrix). Similarly, by tuning the length ratio of A and B while keeping the corona length constant, we observe polymersomes with inner morphology of stripes, gyroid and lamella. The systematic tailoring of all blocks resulted in a combinatorial table of 13 novel multicompartment nanostructures. We obtained each nanostructure in surprisingly high purity (low fractions of other morphologies). For instance, we were able to generate an almost exclusive double helix on cylinder morphology, which inspires cross-linking on topological imprinting of curved cylinders. Several of other morphologies lay the foundation for follow-up research, e.g. double helices on cylinders could template chiral plasmonic materials after mineralization of gold  in the helices, polymersomes with perforated membranes could be interesting for gated release of small molecules, and striped polymersomes allow shape-deformation through topological defects. We currently investigate the underlying self-assembly mechanism in more detail. It is for instance not entirely clear whether self-assembly proceeds via supracolloidal aggregation of precursor micelles followed by structural reorganization, or by micelle formation with subsequent microphase separation inside the core. The first mechanism relates to clustering of patchy particles which is supported by the observation of spherical clusters that grow to patchy cylinders, where the latter mechanism is supported by the transition of patchy cylinder to double helices on cylinder by fusion of the spherical patches.

Figure 4. Co-assembly of patchy micelles to complex MCMs with up to 5 different compartment chemistries in precise geometric location

For our most complex multicompartment nanostructures so far, we combined several patchy precursor micelles within one superstructure while controlling the composition and location of each component. This concept relies on the formation of patchy micelles with specific growth direction and compatible patches. Since the core of the precursor micelles does not participate in the supracolloidal aggregation, its chemistry is irrelevant and can be chosen freely. Further, aggregation is directed by the compatible patches, and precursor micelles with come together in selective solvents. This way polymers ABC and ADC will be located in the same superstructure. By mixing patchy micelles that grow linear with those that form spherical clusters, the location of both units can be precisely controlled. For instance, properly tuned sizes of spherical AB micelles will attach to linear ADA micelles with precise numbers at A parts of ADADADADADA strands. We could show that comparably small AB micelles attach exactly 8 times in form of rings around the linear segment, while medium-sized AB particles attach only once and AB micelles with similar size as ADA micelles only at the very end of the supracolloidal chain. This supracolloidal aggregation could be directed also in 2D lattices at interfaces, and together with inorganic nanoparticles hybrid co-assemblies.
These materials are mostly studied for their potential as multifunctional delivery vehicles in nanomedicine. However, the nanoscale compartmentalization could be beneficial for a range of other applications as well.

Confinement Assembly

The self-assembly of block copolymers in bulk and solution has been the focus of interest for several years. More recently, assembly in confinement has emerged as an additional direction to create non-equilibrium morphologies. Typically, an AB diblock copolymer is emulsified in a water-immiscible solvents and allowed to dry out inside the spherical confinement of the emulsion droplet. This process then leaves behind microparticles with microphases according to the combined effect of microphase separation and curvature. ​
Confinement Assembly

Figure 2: Confinement assembly. The polymer is dissolved in a low-boiling organic solvent and emulsified in water. The organic solvent evaporates leaving behind the water-insoluble polymer. During concentration the block copolymer starts to microphase separate. The final morpholopy is influenced by the block lengths and the curvature. ​

With quite much research in the last 10 years, the confinement assembly of AB diblock is fairly well understood. We thus go one step further and study the confinement-assembly of special polymer architectures and polymer chemistries, e.g., ABC triblock terpolymers, polymer brushes, miktoarm stars, biodegradable or crystalline polymers. In collaboration with the polymer nanostructures group in Sydney led by Markus Müllner, we prepared highly ordered multicompartment microparticles from molecular diblock polymer brushes in confinement assembly. The strong interparticle packing resulted in axially stacked lamellae despite the use of only one surfactant, which typically led to concentric onion particles. The polymer architecture thus clearly has an structure-directing effect in confinement.
In current studies, we analyze the behavior of ABC triblock terpolymers in confinement assembly. Results are very interesting and demonstrate the possibility to create novel multicompartment microparticles and after cross-linking novel polymer nanoparticles. more on this coming soon...

Inverse Morphologies: Block copolymer hexosomes

In surfactant and block copolymer assembly, the packing parameter p is a crude estimation for the resulting topology of the formed superstructure based on volume ratios of core and corona forming parts and their induced surface curvature. The most frequent topologies are spheres, cylinders and bilayer sheets/vesicles with the packing parameter steadily increasing from p < 1/3 (sphere) to p = 1 for planar assemblies such as the bilayer sheet. For a special liquid crystalline class of small molecular surfactants also packing parameter p>1 are possible, which lead to fascinating inverse morphologies such as the inverse spherical morphology or cubosome and the inverse hexagonal cylinders or hexosomes. These particles have unusual large interface and open channel systems to the surrounding medium.

Self-assembled Nanoparticles with 3D Surface Topography

Ipec

Figure 5: Introducing topography to nanoparticles via IPEC formation. Cryo-TEM images of nanoparticles in the near-native state: (from left to right) lamellar, cylindrical and spiral microphase oriented perpendicular to the particle core. The schematic images were 3D reconstructions calculated from cryo-tomographies of the respective nanoparticle

Interpolyelectrolyte Complexation (IPEC). Complementary charged ionic polymers (e.g. polyacid and polyamine), come together in water to form coacervate complexes. The release of counterions is the entropic driving force for this complex formation. IPEC formation is convenient to form nanoparticles with polyionic shell, layers or multiple layers. We theorized that IPECs between corona brushes and homopolymer or block copolymer chains could be used to transform the peripheries of particles or surfaces into 3D surface reliefs or topographies. In the first proof-of-principle work and in collaboration with researchers from Aalto University and University of Jena, we prepared block copolymer micelles with an extensive polyanionic corona brush and grafted this corona through ionic complexation with a PEO-b-polycationic polymer to give a brush-on-brush system. High chain crowding within the particle periphery resulted in unusual microphase separation, where morphologies orient perpendicular to the particle core, i.e. IPEC cylinders and lamellae stand upright on the curved surface separated by PEO/water. The snapshots in Figure 2 were recorded on a 300kV cryogenic transmission electron microscope (cryo-TEM) that visualizes the particles in the near-native solvent-swollen state. The relatively high acceleration voltage thereby reduces beam damage and allows recording a tilt series of images at varying angles. After image alignment to a tomography we calculate a 3D reconstruction of the observed area as depicted in the schematics. The 3D reconstruction gives valuable structural details and insight into the distribution of the polymer phases. From volumetric calculations we found that the observed morphologies follow classical rules of microphase separation, i.e. at volume fraction of about 20vol% IPEC we obtained cylinders and at about 45vol% we obtained standing lamellae. Interestingly, the standing lamellae often formed an IPEC spiral surrounding the core attributed to the substrate topology (curvature).
In follow-up works, we utilized anisotropic core material and grafted polyanionic brushes from the surface of cellulose nanocrystals (7 nm x 120 nm). The same complexation concept then led to nanostructuring of the surface brush, however, the thin rod-like nanoparticles direct the microphase separation into helical morphologies. These helixes consist of an IPEC lamella separated by a PEO/water phase. Other anisotropic substrates such as polymer brushes with a polyanionic shell also allow the structuring of the periphery through IPEC formation. There IPEC discs stack in perpendicular direction to the extensive brush backbone (< 1µm) forming well-defined polymer nanowires.
These examples support the idea that IPEC formation could become a universal tool to transform the surface of interfaces and objects into 3D pattern with specific topographic features and chemistries. The capabilities are currently researched in our group.

Relevant Publications

34.  T. Pelras, C.S. Mahon, Nonappa, O. Ikkala, A.H. Gröschel, M. Müllner*, “Polymer Nanowires with Highly Precise Internal Morphology and Topography”, JACS, 2018, 140 (40), 12736–12740.
30.  T.-L. Nghiem, T.I. Löbling, A.H. Gröschel*, " Supracolloidal chains of patchy micelles in water”, Polym. Chem., 2018, 9, 1583-1592 (invited article and Back Cover of “Emerging Investigators”)
25.  A.H. Gröschel*, A. Walther*, “Beyond the crew cut: Block copolymer micelles with inverted morphologies, Angew. Chem. Int. Ed., 2017, 37, 10992–10994.
23.  J.-M. Malho, M. Moritz, T.I. Löbling, J. Majoinen, Nonappa, O. Ikkala*, A.H. Gröschel*, Rod-Like Nanoparticles with Striped and Helical Topography, ACS Macro Lett., 2016, 5, 1185−1190.
22.  T.I. Löbling, O. Ikkala, A.H. Gröschel*, A.H.E. Müller*, “Controlling Multicompartment Morphologies of ABC Triblock Terpolymers through Post-Polymerization Modification”, ACS Macro Lett., 2016, 5, 1044−1048. (Cover of September issue).
20.  Rational design of ABC triblock terpolymer solution nanostructures with controlled patch morphology T. I. Löbling, O. Borisov, J. S. Haataja, O. Ikkala*, A. H. Gröschel*, A. H. E. Müller* Nat. Commun., 7:12097 doi: 10.1038/ncomms12097 (2016).
15.  Hidden structural features of multicompartment micelles revealed by cryogenic transmission electron tomography T.I. Löbling, J. Haataja, C. Synatschke, F.H. Schacher, M. Förtsch, A. Hanisch, A. H. Gröschel* and A. H. E. Müller* ACS Nano, 2014, 8, 11330–11340.
13.  A.H. Gröschel*, A. Walther, T.I. Löbling, F.H. Schacher, H. Schmalz, A.H.E. Müller*, “Guided hierarchical co-assembly of soft patchy nanoparticles”, Nature, 2013, 503, 247–251.
5.  A.H. Gröschel, F.H. Schacher, H. Schmalz, O.V. Borisov, E.B. Zhulina, A. Walther*, A.H.E. Müller*, “Precise hierarchical self-assembly of multicompartment micelles”, Nat. Commun., 2012, 3, 710–717
(Featured in “Approaching asymmetry and versatility in polymer assembly” Science, 2012, 337, 530-531).