Rodriguez-Emmenegger's research group develops synthetic routes to tailor macromolecules and utilizes their molecular topology, self-assembly, confinement, and structural frustration to understand the fundamental principles that govern the rational design of complex macromolecular and supramolecular xenobiotic and hybrid systems that exhibit biological functions and to unleash new functions towards the development of adaptive synthetic biointerfaces and active synthetic cells.
Controlled Radical Polymerization
We employ various types of advanced radical polymerization and click-type ligations to design polymers with controlled architecture, topology, and hierarchical properties, including brushes, combs, and hydrophilic arborescent polymers.
Antifouling and Hemocompatible Interfaces
Our group conceived and implemented the synthesis and characterization of the most antifouling and hemocompatible polymer brushes known to date. A strong focus lies on understanding the underlying principles in protein adsorption, its prevention, as well as its exploitation for advanced functions. Currently, we work on the development of artificial fibrinolysis on the membranes of artificial lung assists to minimize the need of anticoagulants during patient oxygenation, in order to reduce the high risk of hemorrhages. We also develop readily applicable antibiofouling coatings for medical devices, indwelling catheters, wound dressings, and implants in collaboration with biomedical companies.
Synthetic Cell Membrane Mimics and Protocells
Towards the generation of protocells and protocellular systems, we currently work on the development of advanced membrane concepts based on dendrimersomes and polymersomes from comb-polymers to establish interactions between artificial and natural cells. In the macromolecular structure and topology, we program short- and long-range interactions, such as the competition between local curvature and line tension, to generate microphase-separated domains (modulated phases) that mimic lipid rafts with the aim of driving division and other rudimentary functions. Besides, our team seeks to utilize such biomimetic membranes as a platform to unravel questions related to primitive cell division and communication.
Superselectivity at Biointerfaces
Biological membranes interact with their environment in a very complex manner and can discriminate between almost identical cells or proteins even at extremely low concertation. These interactions are superselective, i.e. the binding is specific, occurs only above a certain threshold density of receptors, and increases supralinear with their density. Nature builds superselectivity, relying on two seemingly opposing principles: extremely high binding constant toward the desired object and general repellency to other objects in spite of the ubiquitous presence of attractive interactions in water.
In our work, we address the question: How can artificial superselectivity be accomplished in synthetic cell membrane mimics? Not only is this important to expand the understanding of biological systems, but also for designing therapeutics able to discern between healthy and abnormal cells differing only in the density of bioreceptors; and to develop synthetic protocells with life-like function. Our concept for superselectivity in synthetic cell membranes requires the integration of (i) specificity, (ii) multivalency (to enhance binding but retain reversibility), (iii) 2D dimensional organization of receptors, and (iv) concepts of cooperativity in binding. To tackle this we have designed and synthesized new types of amphiphiles —comb-polymers and Janus dendrimers— that self-assemble into cell-mimetic vesicles. Although these molecules do not exist in nature, the vesicles formed closely mimic the thickness (only conserved element across all living organisms), flexibility, lateral 2D organization of cell membranes. These properties are precisely encoded in the chemical structure, architecture, and topology of the macromolecular building blocks of the membrane. An example is our recent work, where we discovered that the reactivity of sugar receptors towards lectins is enhanced by the 2D organization of sugars into nanoarrays (clustering) and raft-mimics (cooperativity) on the periphery of protocells. Another example is the endocytosis of living bacteria by a synthetic protocell demonstrates that no active cell machinery is necessary. Besides, this synthetic protocell may serve as the basis for a new generation of smart antimicrobials by introducing a biomimetic mechanism that does not provide a selective pressure leading to the emergence of resistant bacterial strains.