RSA CE&C 2015-2021 Group descriptions

Molecular Systems and Materials Chemistry (MSMC) 43 Research themes Our research activities can be divided into the following four research themes: 1. Artificial cells and organelles Using a bottom-up self-assembly approach, we aim to capture the structural complexity of living cells in artificial architectures. We therefore create nanosized polymer vesicles loaded with catalytic machinery that can be used as nanoreactors (synthetic organelles). These artificial organelles are integrated into multi-compartmentalized structures to mimic eukaryotic cells or with living cells to correct dysfunctional biological processes. 2. Compartments with life-like features We create compartments with the ability to respond to environmental cues, communicate and show transient, dissipative behavior. Of special interest is the design of compartments with motile features (synthetic motors). These motors are also investigated for their ability to engage in biomedical applications through, for example, the active transportation of biologically active compounds. 3. Stimulus-responsive nanoparticles in nanomedicine For effective therapy, the biological activity of particles shouldbe controlled in a spatiotemporal manner. We develop particles that can change their features upon their exposure to specific environmental cues, such as the lower pH or hypoxic conditions found in tumor tissue. 4. Shape effects on biological activity The interaction of nanoparticles with living systems is strongly dependent on their topology. In this respect, shape is underexplored as a determining factor for biological response. We develop efficient shape-changing methods to construct nanoparticles with non-spherical morphologies in order to assess their application potential in biomedicine, from immunology to cancer treatment. Major accomplishments in the evaluation period Our most significant results in the period 2015-2021 are summarized below, covering the four main research themes: 1. Artificial cells and organelles In the recent period, we have developed polymeric vesicles composed of biodegradable amphiphilic block copolymers with the unique feature that the membrane is semipermeable. This has allowed us to incorporate catalytic machinery (i.e., enzymes) inside the lumen of such vesicles and integrate them as nanoreactors with living cells. In particular, we were able to protect patient cells from oxidative stress. 1, 2 We have also investigated possibilities to mimic cells via the construction of multicompartment polymersomes. Polymersome nanoreactors were encapsulated in a larger polymersome, mimicking the structural build- up of a eukaryotic cell as a first approximation. 3 In more recent work, we have investigated the possibility to create a platform which is more reminiscent of the cellular interior. We have therefore investigated the usage of a complex coacervate as an artificial cell platform, mimicking the crowdedness of the cytoplasm. Due to the charged character of the polymer system, proteins could be encapsulated in a highly efficient manner. In order to prevent the coacervates from coalescing, a terpolymer coating was applied, which stabilized the artificial cell platform. This polymer membrane was furthermore shown to be semipermeable, which allowed the transport of small molecules in and out of the coacervate system, making communication between different protocells possible. 4 We have further extended this platform to allow for the controlled uptake and release of proteins, which has now opened up a way to explore these artificial cells in communication with living ones. 5