Invited Talks
Crystallisation
Fibrillation
Rare-earth metal-mediated polymerization techniques as versatile tools towards tunable copolymers
Due to their impressive diversity, the application horizon of thermoplastics is extending far beyond the use as ordinary consumer goods. With the shift from commodity plastics to polymers used in high-tech applications, the precise tuning and modification of these materials is a key requirement. Therefore, the optimization of polymerization catalysts plays a significant role in modern polymer chemistry to efficiently produce different polymer architectures and microstructures for fine-tuning of material properties. Well-investigated rare-earth metal (REM) complexes can act as highly active catalysts in two different coordination polymerization types: Ring-opening polymerization (ROP) of lactones and group-transfer polymerization (GTP) of Michael-type vinyl monomers. Modifications of the complexes were performed to enhance catalyst activity, stereoselectivity and to enable the synthesis of functional block copolymers with versatile end-groups. With the development of these new polymers various aspects of modern polymer chemistry were targeted: Biobased and biodegradable, metal-functionalized, and stimuli-responsive, amphiphilic polymers for drug and nucleic acid delivery.
Ultra coarse-grained modelling of near-crystalline functional polymers: what can we learn?

Inevitably, large-scale computational studies of structure-property relationships in polymers require simplified models, which achieve the necessary efficiency by mapping large groups of actual atoms on single interaction centers. However, the implementation of ultra coarse-grained models can be also very challenging: the significant simplification of the molecular structure can eliminate features that are, in fact, crucial for structure formation. One important class of materials, where such problems are expected, are functional polymers with backbones comprising aromatic rings and small side chains ─ conjugated polymers are a typical case.
Nevertheless ─ and this is one of the main ideas we plan to convey ─ the perspectives of simplified models in studies of such “board-like” polymers are better than one might initially expect. One reason is that these polymers commonly exhibit pronounced structural disorder [1]. Even their crystalline phases can have large para-crystallinity, whereas one often observes [1,2] only small-scale molecular aggregation and liquid-crystalline mesophases. This structural “noise”, combined with the collective nature of the ordering processes, might mitigate the reduction of microscopic details, rendering simplified models useful for addressing certain questions.
First, we will summarize some simplified models used in generic studies of polymer order, crystallization in particular. We will argue why these approaches are insufficient for board-like functional polymers and highlight some simplified models that have been developed for these materials. Next, we will focus on an approach [3,4] where near crystalline, sanidic, mesophases are described by combining a minimalistic representation of polymer architecture with generic anisotropic potentials. As an application, we will present new simulation results related to studies of texture of P3HT films [5] where face-on and edge-on orientation of crystalline lamellae is favored at the bottom and top surface, respectively. These results highlight the need for understanding the elastic properties of highly ordered, almost crystalline, mesophases.
References
[1] Noriega et al, Nature Mat. 2013, 12, 1038-1044.
[2] Stingelin N., Polym. Int. 2012, 61, 866-873.
[3] Greco C., Melnyk A., Kremer K., Andrienko D., Daoulas K. Ch. Macromolecules 2019, 52, 968-981.
[4] Wood E. L., Greco C., Ivanov D. A., Kremer K., Daoulas K. Ch. J. Phys. Chem. B. 2022, 126, 2285-2298.
[5] Dolynchuk O., Schmode P., Fischer M., Thelakkat M., Thurn-Albrecht T. Macromolecules 2021, 54, 5429-5439.
Interface-Induced Crystallization in Polymers: From Model Systems to Functional Semiconducting Polymers
Crystallization is often initiated at interfaces. Understanding the physical process underlying interface-induced crystallization is of fundamental interest and is relevant for many material applications. Interface-induced crystallization of liquids can occur either by heterogeneous nucleation or by the equilibrium phenomenon of prefreezing. First, we present a combined theoretical and experimental study of the effect of substrate-material interactions on the thermodynamics of prefreezing and on the kinetics of heterogeneous nucleation in model polymers on various substrates [1-3]. Second, the knowledge gained about interface-induced crystallization is used to elucidate the role of interfaces for crystal orientation in films of conjugated polymers, which is important for device performance. Using polythiophenes as model conjugated polymers, we show that different crystal orientations can be formed at the interfaces to a substrate and vacuum as a result of two competing interfacial interactions. Our results demonstrate that increasing the polarity of polythiophene side chains influences the interactions at the interfaces, resulting in a change of crystal orientations [4]. Thus, we disclose the crucial role of interfacial interactions for crystallization kinetics, thin film morphology, and control of molecular orientation in films of model and semiconducting polymers.
References
[1] O. Dolynchuk, M. Tariq, T. Thurn-Albrecht, J. Phys. Chem. Lett. 10, 1942 (2019).
[2] M. Tariq, O. Dolynchuk, T. Thurn-Albrecht, J. Phys. Chem. C 124, 26184 (2020).
[3] M. Tariq, T. Thurn-Albrecht, O. Dolynchuk, Crystals 11, 924 (2021).
[4] O. Dolynchuk, P. Schmode, M. Fischer, M. Thelakkat, T. Thurn-Albrecht, Macromolecules 54, 5429 (2021).
Crystallization helps self assembly: Visualizing grain boundaries in block copolymers
Aligned semicrystalline polymers give rise to optical birefringence that results from subwavelength molecular arrangement. Semicrystalline–amorphous block copolymers (BCPs), i.e., those possessing both amorphous and semicrystalline blocks, provide an extension of this principle to self-assembled BCP morphologies. Structure formation in semicrystalline–amorphous BCPs is governed by a delicate interplay between crystallization and microphase separation.[1] If the crystallization temperature Tc of the crystalline block is well below the glass transition temperature Tg of the amorphous block, the semicrystalline block undergoes confined crystallization. However, confined crystallization alone does not ensure a macroscopic alignment of crystallites within the microphase-separated morphology
necessary for optical anisotropy. For this, the crystallite orientation with respect to the interface of the confining morphology, e.g., lamellae[2] or cylinders,[3,4] has to be well-defined. This orientation is a function of Tc: as Tc is increased, the long axis of the polymer chains, the crystallite c-axis, transitions from a random orientation to parallel and then perpendicular with respect to the interface of the polymer blocks, thereby mirroring the microphase-separated morphology.
Confined crystallization and crystal alignment can also take place in three-dimensional BCP networks such as the gyroid.[5] The gyroid is a triply periodic isotropic structure which possesses a constant mean curvature surface.[6] The convoluted gyroid channels form local subhelices of differing radii and
handedness along the ⟨111⟩, ⟨100⟩, and ⟨110⟩ directions which meet at triads throughout the structure. Upon crystallization inside a gyroid, crystallites are therefore confined to tortuous pathways inside a 3D network. My talk focuses on the optical anisotropy of the structurally isotropic alternating gyroid morphology in a
semicrystalline triblock terpolymer. I will show that this optical anisotropy results from a preferential alignment of confined polymer crystallites within one single gyroid network.
[5] I will further illustrate how this enables optical imaging of the gyroid BCP grain structure, which is useful for a rapid optimization of protocols for the annealing of BCP films, ultimately allowing the manufacture of self-assembled gyroids with exceptional long-range order.
References
[1] Wei-Na He, Jun-Ting Xu, Prog. Polym. Sci.2012, 37, 1350–1400
[2] Lei Zhu et al., Journal of the American Chemical Society 2000122 (25), 5957-5967
[3] Huang et al., Macromolecules 200134 (19), 6649-6657
[4] Huang et al., Polymer2006, 47, 5457– 5466 [5] Dehmel et al., Macromolecules 201750 (16), 6255-6262
[6] Dolan et al., Adv. Opt. Mater.2015, 3, 12– 32
Protofibrils vs. cross-β fibrils: Two alternative amyloid assembly types
Amyloid fibrils, in which multiple copies of a protein molecule are stacked along the fibril axis in a highly regular cross-b structure, are a characteristic feature of many diseases. The spreading of these protein aggregates over the affected organ has been linked to disease progression. Under the same conditions that favor cross-b fibril formation, a second amyloid assembly type is formed which is often referred to as protofibril. Protofibrils are also rich in β-structure, but are shorter, less rigid, curvilinear assemblies of oligomeric subunits. Protofibrils formed from amyloid-β peptide (Aβ) may represent the main toxic species in Alzheimer’s disease, as they are more effective than cross-b fibrils at inducing synaptic dysfunction and triggering inflammation. In November 2022, phase III clinical trial data for an anti-protofibril monoclonal antibody reported it to be the first drug to slow mental decline in a robust clinical trial. Here we elucidate the mechanism of protofibril formation, identify physiological conditions that promote protofibril assembly, and identify the interplay between protofibrils and cross-β fibrils. We find that protofibrils form comparatively fast and antagonize their replacement by cross-β fibrils both by competing for monomers and by blocking secondary nucleation sites for cross-β fibril formation. The critical protein concentration required for protofibril formation can be reached in acidic conditions as present in endosomes/lysosomes.
Virulent and Antimicrobial Amyloids in Infections and Neurodegeneration
Amyloids are protein oligomers and fibers which are known mainly in the context of neurodegenerative diseases yet are secreted by species across kingdoms of life to carry out physiological function and help survival and activity. Their function as key virulence factors in microbes has rendered them attractive candidates for structural characterization aimed at discovering novel antivirulence therapeutics. Our laboratory pioneered the atomic-level analysis of bacterial amyloids and eukaryotic functional fibrils involved in cytotoxicity, biofilm structuring, and antibacterial activity. Our findings thus far exposed an extreme structural diversity, extending beyond canonical amyloid cross-β structures, and encoding different activities. In particular, the discovery of a novel class of cross-α amyloid fibrils of toxic peptides presented a unique protein architecture, offered drug targets and leads, and opened a fresh perspective to study amyloid-related toxicity. Moreover, we revealed that amyloids secreted by bacteria show similarities in molecular structures to human amyloids involved in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This might raise concerns about the involvement of microbes in facilitating these diseases, similar to prion proteins transmitted by contaminated meat that elicit the Creutzfeldt-Jakob disease. In addition, we identified peptides produced across species that provide antimicrobial protection that form amyloid fibrils and determined their first high resolution structures. This amyloid-antimicrobial link proposes a physiological role in neuroimmunity for human amyloids. Such antimicrobial fibrils can facilitate the design of functional and stable nanostructures to serve as a stable coating for medical devices or implants, industrial equipment, food packing and more.
Self-assembly of conformationally ordered and disordered polypeptide and protein-based copolymers
En route for highly functional biomaterials and nanodevices, amphiphilic block copolymer structures are gaining in complexity and precision in their macromolecular structure. In addition to their intrinsic self-assembly properties, they may include stimuli-responsiveness possibly in addition to relevant biological functions. By combining the self-assembly properties of block copolymers together with the richness of function-bearing peptides, polypeptide and proteins, we aim at creating functional biomaterials. We are interested in designing copolymers able to self-assemble into well-defined micelles and vesicles that can advantageously be loaded with drugs and present a surface with multivalent presentation of bioactive building blocks that were shown to target specific cell receptors. We will especially focus on how the conformation and responsiveness of polypeptide-based materials can allow deep control in self-assembly processes.
Bioinspired Polymer Surfaces: From Structure-Property Relationships to Biomedical Applications
Secondary nucleation in amyloid formation
Secondary nucleation is a critical step in many self- assembly processes including crystallization and amyloid fibril formation. In several systems, including amyloid β peptide and protein tau from Alzheimer’s disease, α-synuclein from Parkinson’s disease and IAPP from diabetes type II, the process is associated with the generation of toxic species. A molecular level understanding of secondary nucleation may thus be important towards the design of inhibitors to combat these devastating human diseases. Our studies aim find the molecular driving forces that govern secondary nucleation and to understand this process in terms of its composite steps and structural transitions. The talk will give an overview of our current knowledge and unknown aspects about secondary nucleation and aims to open a discussion on how to address this using experiments, simulations and theory.
Rate-limiting processes in protein self-assembly: from the test tube to living systems
In the past decades, the central role of aberrant protein self-assembly has been established in many neurodegenerative diseases. The molecular mechanisms that underlie this process of protein aggregate formation have been studied in detail under controlled in vitro conditions. However, connecting the fundamental physical properties of protein self-assembly to the formation and proliferation of protein aggregates in the brains of affected individuals remains a key challenge in the field. I will show how, starting from a knowledge of the underlying physics, we build simple coarse-grained mathematical models that are able to describe the temporal and spatial distribution of aggregates in the brains of lab animals and human patients, linking back to the underlying molecular processes. These minimal models not only provide a qualitative understanding of the ranges of possible behaviors but also allow quantification of the relative importance of different classes of processes in protein self-assembly in vivo. I will show how the application of these models can establish the mechanism of prion self-replication in mice and identify the rate-limiting process in the appearance of tau aggregates in Alzheimer’s disease.
Stacks of Correlated Lamellar Polymer Crystals
Based on the mechanism of self-induced nucleation, the orientation of polymers in the basal lamellar crystal can propagate to other lamellae growing on top [1,2]. As a result, stacks of crystalline lamellae all having a uniquely oriented shape, referred to as “3D (three-dimensional) single crystals”, can be obtained [3]. Using a rationally designed two-step crystallization approach, we were able to induce the formation of stacks of superposed and uniquely oriented flat-on polymer lamellae exclusively and controllably at the periphery of mono-lamellar polymer crystals [4]. We employed this approach for the formation of a “fence” of stacks of lamellar crystals at the periphery of mono-lamellar stereocomplex single crystals of poly(l-lactide) and poly(d-lactide). The resulting morphology resembled a “pseudo hollow crystal” with an almost empty interior of a size controllable by crystallization time. We believe that the presented growth mechanisms leading to “3D single crystals” can be observed for all crystallizable polymers including block copolymers.
References
[1] H. Zhang, M. Yu, B. Zhang,R. Reiter, M. Vielhauer, R. Mülhaupt, J. Xu, and G. Reiter, Phys. Rev. Lett. 112, 237801 (2014).
[2] S. Majumder, R. Reiter, J. Xu, and G. Reiter, Macromolecules 52, 9665– 9671 (2019).
[3] Z. Guo, S. Yan, and G. Reiter, Macromolecules 54, 10, 4918–4925 (2021).
[4] W. Chen, B. Bessif, R. Reiter, J. Xu, and G. Reiter, Macromolecules 54, 8135–8142 (2021).
Flow-Induced Crystallization Polymers Across the Spectrum of Backbone Rigidity
Processing of thermoplastics during injection molding and blow molding usually includes melt flow followed by rapid cooling at rates up to 103 K/s and solidification at high supercooling. Fast scanning calorimetry (FSC) is able to cover high processing rates and wide temperature windows by just using a few nanograms of the sample. In reality, polymers of all types are subject to melt processing and the resulting conditions oftentimes result in Flow Induced Crystallization (FIC). This presentation will systematically consider FIC in a series of polymers with increasing backbone stiffness and inter/intramolecular interactions. Coupling FSC with other techniques, including micro-IR spectroscopy, atomic force microscopy, polarized optical microscopy, and X-ray computed tomography the kinetics, polymorphism, and morphology transition associated with FIC will be discussed for polyolefins, polyamides, poly (ether ether) ketone and its composites. In addition, the role of the nematic phase on FIC in rigid backbone polymers will also be discussed.
Melt memory of semicrystalline polymers: The effect of intermolecular interactions
The crystallinity of polymers is decisive in the final properties such as mechanical performance or biodegradability. The thermal properties depend, among others, on the molar mass of the polymer, the chemical structure or the presence of heterogeneities.
Another factor that affects the thermal properties is the thermal history. The material has to be heated well above the melting temperature to erase the thermal history. Otherwise, if the applied temperature is not high enough some self-nuclei can survive which affects the crystallization process. When this occurs there is an increase of the crystallization temperature and an acceleration of the crystalline process. This is known as the melt memory effect.
The results reported in literature show that some polymers have a wide melt memory effect such as polybutylene succinate whereas others have a very weak melt memory such as polyethylene.
In order to understand these differences a systematic study of the effect of intermolecular interactions on melt memory has been carried out. For that several polymer families have been studied varying the functional group, including polyamides, polyesters, polyethers or polycarbonates. More recently, the effect of incorporating additional functional groups to polyesters has been studied. The obtained results show a correlation of intermolecular interactions with melt memory for aliphatic homopolymers.
Effects of in vivo conditions on protein aggregation:computational approaches
The aggregation of proteins into β-sheet structures has been extensively studied in vitro underconditions that are far from the physiological ones. There is need to extend these investigationsto in vivo conditions where protein aggregation is affected by a myriad of biochemical interac-tions. As a hallmark of numerous diseases, these self-assembly processes need to be under-stood in detail to develop novel therapeutic interventions. The aim of our work is to elucidate theeffects of various in vivo components and conditions, such as the presence of metal ions, oxida-tive stress, an acidic environment mimicking tissue inflammation, the presence of cell mem-branes and the brain extracellular matrix on the conformational dynamics and aggregation of theAlzheimer’s disease-related amyloid-β peptide. To this end, we develop multiscale simulationapproaches, perform large-scale molecular dynamics simulations, and establish novel analysistools allowing us to unravel the aggregation pathways under varying external conditions. Themost recent and enlightening results from these simulations will be presented in my talk.