In this project, we will investigate the interactions of soft microgels in the size range of 40–500 nm radius with cells. We aim to gain a conceptual understanding of how microgel properties affect their adsorption to cell surfaces as well as their translocation into cells and, ultimately, their fate inside the cell. We will initially use human embryonic kidney (HEK293) and immortal human cervical cancer cells (HeLa) as both are representative and well-described human cellular model systems. Depending on the progress of parallel SFB projects, we are prepared to include additional relevant cell types in our experimental portfolio.

Living cells and tissues are constantly subjected to mechanical stress and wear stimulating biological processes, such as the signaling of pain. Researchers strive to explore these biomechanical interactions but are confronted with a lack of tools to visualize stress from within the cell up to the tissue scale. The goal of this project is to develop molecular moieties by synthetic chemistry that act as predetermined breaking points either sending out an optical signal or initiating a biochemical reaction once subjected to stress. This will allow the spatial and directional optical resolution as well as the harnessing of force effects down to the molecular level. Initially, the optical probes will be incorporated into cell-like polymer architectures that resemble certain features of cells. This will not only allow the controlled benchmarking of the probes but moreover to learn about the response of these cell-like systems to mechanical stress. Subsequently, employing the optical stress-sensors in living cells will elucidate mechanical cellular responses in a much more complex, natural environment. Beyond the sensing of stresses, the initiation of biochemical reactions in cell-like nanoreactors employing force-cleavable protecting groups will lead to bioinspired materials that can perform functions nature has not yet achieved.

Despite the sophisticated and well-established combinations of matrix and filler components, sharply defining the molecular structure - macroscopic property relationships of nanocomposites remains far from being a straightforward process even today. This complexity stems to a high degree from the intricate interactions taking place at the exact contact point of the individual materials, i.e. their interface. Yet, the mechanical properties of nanocomposites that come to define their suitability and, thus, applicability, are particularly affected by the properties of this interface.

Mechano-optical molecular force probes (mechanophores) can shine light on this matter by visualizing critical mechanical stresses and strains through changes in their color and/or luminescence. By covalently integrating mechanophores into the structure of macromolecular materials, we can track precisely where, when, and to what extent a polymer nanocomposite material is exposed to mechanical stress. This will contribute to a better understanding of the molecular causes of the mechanical properties of polymer nanocomposites, and will ultimately improve their molecular hierarchical properties and thus their resilience by reliably displaying the critical load thresholds before the material fails.

By laying the foundations for the development of a molecular-scale fractography technique, based on confocal laser scanning microscopy and super-resolution nanoscopy that probes beyond and beneath the fracture surfaces of materials, the former trial-and-error character of the optimization of high-performance polymer nanocomposites can be further redefined as results can be effectively exploited to verify the already existing computational mechanical simulations.

The damaging and failure of macroscopic polymeric materials can generally be attributed to covalent bond scission, a nanoscopic event. Hence, the observation and quantification of mechanical stress on the nanoscale is a major challenge to identify the molecular origin of polymeric materials' macroscopic behavior under load. Recent successes in the development of novel optical force probes have proven that photochromic compounds, such as spiropyran, azobenzene, or hexaarylbiimidazole, can be employed as efficient molecular force sensors. Thus, the investigation of other photoswitches is bound to lead to improved understanding of the mechanochemical reaction pathway and promises access to superior optical force probes. With this project, I want to investigate the action of mechanical stress on diarylethene-type photoswitches incorporated into polymeric architectures. Not only will this work explore the unprecedented mechanical activation of pericyclic reactions involving a 6π-electron system thus considerably contributing to the understanding of these reactions' pathways, but moreover try to establish diarylethenes as superior optical force probes that - contrarily to the popular spiropyran motif - are not thermally labile and as such can prospectively be used to quantify forces independent of time. Beyond their potential as superior force probes, these diarylethenes could moreover exhibit improved ring-opening efficiency under stress as compared to the generally inefficient photochemical pathway. This exploration of the interface of mechanical stress and light thus is highly likely to answer unsolved questions in each of the respective research areas and contribute considerably to their advancement.