Hierarchical Supramolecular Architectures: Towards a Model of the Cytoskeleton

Cells exhibit outstanding multi-functional properties and sophisticated organization within a micro-scaled environment. Within the cell, there is a cellular architecture called the cytoskeleton, which is assembled from protein monomers, which provides mechanical support, and which generates the shape of cells and is involved in intracellular transportation. Insights into the cytoskeleton have sparked a lot of development in synthetic biomimetic systems.

This dissertation aims to develop a cytoskeleton-like supramolecular system, with the long-term vision to achieve several structural, mechanical, and dynamic functions of the cellular cytoskeleton. The system integrates self-assembled fiber formation, external triggers, biomolecular recognition, and compartmentalization to build up hierarchical supramolecular mimics of the cellular cytoskeleton.

There are three main tasks for the design of mimics of the cytoskeleton: designing and synthesizing adequate mimicking materials, implementing these into cell-mimetic compartments, and affecting and interacting with their functions. First, we developed a supramolecular polymer system that could self-assemble into tubular architectures in water and introduced biomolecular recognition to induce the hierarchical assembly of the supramolecular nanotubes. Depletion forces have been applied to form hierarchical supramolecular bundles and mimic the crowdedness of the intracellular environment. Finally, we chose the giant unilamellar vesicle as a compartment to incorporate these architectures for building up a cell-like model. The inverted emulsion method has been chosen to encapsulate the architectures into the vesicles for achieving the mimic of the cellular cytoskeleton. Dynamic behavior of the supramolecular bundles and networks has been observed upon external triggers, such as light, depletion forces, and changes in environmental factors. These methods resulted in changes of the supramolecular architecture and/or the surrounding vesicle and affected their interaction and morphology.

In overview, this thesis has introduced two novel hierarchical supramolecular architectures as rudimental cytoskeleton models. By introducing biotin-streptavidin conjugates and depletion forces, hierarchical supramolecular polymer systems can be obtained in a tunable way, with crosslinking and interfacing capabilities. Furthermore, we encapsulated hierarchical architectures into cell-sized compartments, which takes a crucial step forward to mimicking the cellular cytoskeleton.