Polymers under Multiple Constraints: Restricted and Controlled Molecular Order and Mobility

This virtual issue collects articles originating from the Collaborative Research Center/Transregio (CRC/Transregio) TRR 102 that was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation) from 2011 to 2023. The CRC was a joint activity between the Martin Luther University Halle-Wittenberg and Leipzig University. Furthermore, projects from several neighboring research institutions were included. Its title, “Polymers under multiple constraints: Restricted and controlled molecular order and mobility”, reflects the fact that in macromolecular systems the formation of structural order on the monomer scale is a complex process as it is constrained by its environment due to the connectivity of the polymer chain. In the CRC such processes of structure formation and self-assembly were investigated, in which molecular structures and dynamics are affected by chain connectivity and additional constraints such as specific interactions, external forces, geometrical confinement, crowding, or topological restrictions. Two outstanding examples of such ordering processes and central topics of the CRC are the crystallization in the field of synthetic polymers and the formation of amyloids in the field of proteins. The comparison of these two fields targeted by the CRC has finally led to new studies on hybrid polymer systems containing molecular elements that are representative of both synthetic and biological macromolecules during the last funding period. Polymer crystallization is a well-established field, yet consensus on crucial aspects has not yet been achieved, particularly regarding the mechanisms leading to the formation of semicrystalline morphologies that ultimately determine the mechanical properties. Moreover, given that polymer crystallization results in hierarchical structures spanning across multiple length scales, it is obvious that constraints as mentioned above play a significant role. Until today, a comprehensive understanding of structure formation under processing conditions and of the intricate relationship between microscopic structure and mechanical properties remains limited. It is hoped that more fundamental understanding in this field can contribute to a knowledge-based transition from today's commodity polymers to modified or new designs that are more amenable to recycling and can be produced in a more sustainable way. Amyloids fibrils, as linear protein aggregates, are known to be associated with neurodegenerative disorders but also exist as functional aggregates. They consist of (mis)folded proteins and share the partial order on the local scale, the nucleation and growth of larger scale structures during ordering, and the appearance of universal features with semicrystalline polymers. Physicochemical research predominantly focuses on deciphering the underlying mechanisms of aggregation, studying intermediate states, and the intricate interplay between local structure and specific interactions, aggregate morphology, and kinetic processes. Although the CRC's research in the area was not directly aimed at medical impact, it is hoped that fundamental knowledge will provide a helpful background for research that directly addresses medical and pharmacological issues (Figure 1). The following is a brief overview of the articles in this virtual issue, which comprises a number of research articles, perspectives and reviews, published recently in Macromolecular Chemistry and Physics, Macromolecular Bioscience, and Macromolecular Theory and Simulations that report on the results obtained within the CRC and attempt to place these results in a broader context of related research. The review by Kay Saalwächter and co-workers (macp.202200424) gives an overview of recent developments concerned with elucidating the semicrystalline structure formation during crystallization from bulk polymer melts, with a focus on factors that have received less systematic attention before. Effects of the presence or absence of chain motion through the crystallites or of entanglements on the morphology were specifically addressed in the CRC. On the theoretical side an effort was made to analyze the driving forces for chain crystallization in equilibrium simulations using advanced methods in Monte Carlo simulations. Analysis of the thermodynamics of single chain transitions allowed to work out similarities and differences to protein folding. The article by Kay Saalwächter, Thomas Thurn-Albrecht, and co-workers (macp.202200459) shows that polybutylene succinate lacks the above mentioned intracrystalline molecular dynamics and in fact exhibits the typical morphological features previously found in model polymers for this case. In the article by Mario Beiner and co-workers (macp.202200433), the structural features of a series of a high performance aliphatic polyamides with longer methylene sequences are examined, focusing on the existence of different polymorphs and effects of flow. The subsequent two papers are concerned with nucleation, the process by which crystal growth is initiated. Wycliffe Kiprop Kipnusu and co-workers, in article macp.202200443, use a new combination of experimental techniques, namely fast scanning calorimetry (FSC) and Fourier transform infrared (FTIR) spectroscopy to follow the evolution of the calorimetric properties and of the molecular interactions during homogeneous nucleation in quenched amorphous polyethylene terephthalate (PET). While homogenous nucleation typically prevails at large supercooling, crystallization is commonly induced at interfaces at higher temperatures, which is usually subsumed under the term heterogeneous nucleation. The perspective “On Thermodynamics and Kinetics of Interface-Induced Crystallization in Polymers” by Oleksandr Dolynchuk and Thomas Thurn-Albrecht (macp.202200455) summarizes the differences between heterogeneous nucleation and the alternative process of prefreezing. The direct observation and a theoretical description of the latter process was achieved within the CRC, and typical features were explored establishing a new basis for the description and analysis of the initial stages of interface-induced crystallization. The article by Jörg Kressler and co-workers (macp.202200428) deals with a special case of polymer crystallization under 2D confinement, namely at the surface of water. Here specifically the influence of tacticity of poly(methacrylic acid) on structure formation is investigated. In the article by Martin Tress and co–workers (macp.202200452), crystallization under 3D confinement in small droplets is studied by a new experimental approach using nanostructured electrodes in dielectric spectroscopy. The research in the CRC also targeted the development of new advanced simulation methods. An example is documented in the article by Stefan Schnabel and Wolfhard Janke titled “Monte Carlo Simulation of Long Hard-Sphere Polymer Chains in Two to Five Dimensions”, in which a very efficient off-lattice simulation method is applied to a classical problem of polymer physics (mats.202200080). Christian Lauer and Wolfgang Paul, in article mats.202200075, use a coarse-grained protein model and Monte Carlo simulations to study folding and aggregation of polyglutamin, which is supposed to play an important role in Huntington's disease, a hereditary neurodegenerative disease. Atomistic molecular dynamics simulations comparing different force fields are used to understand the incorporation of n-alkanes into phospholipid bilayers in the article by Anika Wurl and Tiago M. Ferreira (mats.202200078). “Thermoplasmonic Manipulation for the Study of Single Polymers and Protein Aggregates” by Frank Cichos and co-workers is a method-oriented perspective article that reviews fundamentals and applications of thermoplasmonic manipulation with special emphasis on the trapping and manipulation of single macromolecules and peptide aggregates (macp.202300060). The perspective concludes with an overview of the variety of hydrodynamic effects that can be advantageously used alongside thermo-osmosis to yield a new field of thermofluidics. Based on an extended series of NMR experiments complemented by other experimental methods, Benedikt Schwarze and Daniel Huster (mabi.202200489) give a comprehensive overview of how mutations at single sites can contribute to the understanding of amyloid 𝜷1-40 structure formation. Structure formation on different length scales is investigated in combination with studies of fibrillation kinetics and toxicity assays. The review by Torsten John, Lisandra L. Martin, and Bernd Abel (mabi.202200576) focuses on combined experimental and theoretical work based on MD simulations to elucidate the role of interfaces in amyloid fibrillation, for which both accelerating as well as inhibitory effects on peptide self-assembly have been observed. A specific example of an interfacial effect is studied in the research article by Wolfgang H. Binder and co-workers (mabi.202200522), which addresses the inhibition of amyloid 𝜷1-40 fibrillation by different hybrid lipid–polymer vesicles. While most in vitro experiments on amyloid formation are naturally performed in dilute solution, Maria Ott and co-workers set out to explicitly study effects of crowded environments on fibrillation using a combination of bulk and single molecule optical methods in their article (mabi.202200527). In contrast to the prominent disease-related amyloids, more and more so-called functional amyloids have been discovered and studied recently. These are non-toxic protein assemblies that fulfill a specific biological function, such as storing hormones. An example is the parathyroid hormone PTH84 whose fibrillation and intricate concentration-dependent nucleation behavior is examined in the research article by Jochen Balbach and co-workers (mabi.202200525). The stability of the human eye lens 𝜸D-crystallin protein in solution at the high concentrations in the eye lens is a prerequisite for its transparency. Loss of stability leads to cataract. In article mabi.202200526, also by Jochen Balbach and co-workers, the authors study its chemical and conformational stability under UV-irradiation. Another area where conformational transitions of proteins are potentially important are coiled coils, a self-assembled structure consisting of several 𝜶-helices, which can undergo a transition to a 𝜷-sheet structure when subject to tensile or shear deformation. Ana Vila Verde, Kerstin G. Blank, and co-workers (mabi.202200563), describe microscopic shear experiments conducted with an atomic force microscope on model coiled coils and compared their results to simulations. The last two articles are concerned with the fusion of synthetic polymer elements with peptide elements into new hybrid synthetic/peptide polymers. The extended review “Secondary Structures in Synthetic Poly(amino acids): Homo- and Copolymers of Poly(Aib), Poly(Glu), and Poly(Asp)” by Wolfgang H. Binder and co-workers (mabi.202200344), gives an overview on secondary structure formation of several peptide homopolymers and surveys studies performed within the CRC on artificial hybrid polymers that can be used as model polymers for amyloid-type fibrillation processes. The concluding research article by Daniel Sebastiani and co-workers (mats.202200070) reports on specific hybrid polymers. Molecular dynamics simulations are used to investigate how the secondary structure formation of homopeptides in water is suppressed by the insertion of short polyethylene segments. We thank all investigators of the CRC for their contributions to this issue and for the fruitful spirit of cooperation during the course of the whole project. On behalf of all the participants of the TRR 102 (Project-ID 189 853 844 – TRR 102) we thank the Deutsche Forschungsgemeinschaft for their major support, the Martin Luther University Halle-Wittenberg and Leipzig University for their additional support, and Wiley-VCH for the opportunity to publish this virtual issue. The authors declare no conflict of interest. Frank Cichos has been a professor for molecular nanophotonics at Leipzig University (Germany) since 2007. He studied physics at Chemnitz University of Technology. After completing his Ph.D. in the group of Prof. C. von Borczyskowski at Chemnitz University of Technology, he conducted postdoctoral research at the Universitè de Bordeaux I (France) and Chemnitz University of Technology. His current research interests comprise the optical manipulation of single molecules with dynamic temperature fields, thermofluidics, and the nonequilibrium physics of synthetic active matter. Thomas Thurn-Albrecht has been a professor of experimental polymer physics at the Martin-Luther-University Halle-Wittenberg (Germany) since 2003. He studied physics at the University of Freiburg (Germany) and Edinburgh University (UK). After completing his doctorate with Prof. G. Strobl at the University of Freiburg in 1994, he conducted postdoctoral research at the Max Planck Institute for Polymer Research (Germany) and the University of Massachusetts (USA). His current research interests focus on X-ray scattering on polymer systems, semicrystalline polymers, and structure of semiconducting polymers.