Multicomponent systems formed by reversible non-covalent interactions are a key signature of biological matter with supramolecular fibers as important components. Often sophisticated structures require the association between components with high structural diversity like the cell membrane, which consists of phospholipids, proteins and cholesterol. Their systems’ specific properties emerge from a complex interplay of the manifold of orthogonal and specific interactions. Along this line, the design of synthetic well-organized multicomponent systems in water has attracted increasing interest in the last decade. Although this field is still in its infancy, several examples have highlighted its potential in biomedical applications. Moreover, the study of complex, synthetic molecular systems has advanced our understanding of biological systems.
In our group we explore the many options of specific supramolecular polymers in water based on a strong fundamental basis with the main aim to arrive at functional biomaterials. Although many aspects can be studied, we focus on the interplay between structure, dynamics and function of novel multicomponent supramolecular polymers and assemblies. Both as a model and an attractive target, we introduced supramolecular polymers based on water-soluble benzene-1,3,5-tricarboxamide amphiphiles (BTAs). We use a large variety of techniques to study the interplay between structure, dynamics and function. Within this research topic, we have three research directions that are highly interconnected.
Fundamentals of supramolecular polymers in water.
High resolution cryogenic transmission electron microscopy (cryo-TEM) gives us detailed insights in the structure of our supramolecular assemblies in water. Surprisingly, we observed that most of the BTA-based supramolecular polymers are double helices, where the pitch can be tuned by copolymerization. In some other cases micelles or sheets are formed and it is still a real challenge to predict the morphology formed based on the molecular structure. Next to structure the dynamics are equally important, and we introduced the idea of studying the kinetics using hydrogen-deuterium exchange followed by mass spectrometry. These data showed a diversity in stability within the assemblies which can range from exchange of monomers in hours to exchange in days.
By understanding in detail, the relation between molecular structure, supramolecular structure and dynamic behavior in water of different structures and co-polymers, we go step-by-step to highly functional biomaterials that mimic the functions of the extracellular matrix.
Multivalency with focus on copolymers and their dynamic interactions with biological matter.
The simultaneous interaction of multiple ligands to multiple receptors is a key element in biology. Hence, it does not come as a surprise that many groups are interested to make use of this multivalent effect and try to fully understand this behavior. In case of supramolecular polymers, the ligands are intercalated as a comonomer in a stochastic, though dynamic manner in the polymer. As a result, it should be possible to reorganize the ligands once in contact with receptors. This could lead to dynamic reciprocity with unexpected results for artificial biomaterials. Different supramolecular ligands as well as ligands able to bind via dynamic covalent chemistry are incorporated in supramolecular polymers, which in turn are investigated for their interactions with receptors on supported liquid bilayers as well as with receptors on the cell surface. The studies are focused on a full understanding of the multivalent effects in dynamic supramolecular polymers, but hopefully also lead to novel biomaterials.
Responsive hydrogels and functional biomaterials.
In order to arrive at functional biomaterials, it is not only important to synthesize and study the assembly process of novel building blocks. For applications it is necessary to create materials and more specifically hydrogels. The group is studying novel concepts to adaptive and responsive materials by using multicomponent systems. One of the strategies is to combine supramolecular polymers with macromolecular polymers, both covalently and non-covalently.
