Welcome to the Supramolecular & Biomaterials Chemistry group

Coiled-coil chemistry1.JPG

Figure 1. Coiled-coil chemistry in the Kros laboratory. Left panel shows examples of peptide mediated self-assembly and the right panel shows examples of how coiled-coil assemblies are utilized in new functions.

The Supramolecular & Biomaterials Chemistry group of Prof. Alexander Kros is active in the field of self-assembly of amphiphilic peptides and applying them in supramolecular chemistry.
A common theme in these materials are peptides (< 25 amino acids) that can adopt specific secondary structures to control the behavior of the entire assemblies. We have described in several reviews the use of de novo designed peptides and engineered proteins as components in bio-nanotechnology. Since 2008 we have a published a number of publications in which a heterodimeric coiled-coil motif has been successfully used to design non-covalent and reversible triblock copolymers that assembled in different micellar structures. Furthermore we have developed polymersomes based on a coiled-coil motif which is successfully used a carrier for flu vaccines. Dr. Kros received an ERC starting grant (2009) for the development of a model system for membrane fusion inspired by the naturally occurring SNARE protein machinery. This is the first model system for membrane fusion that has all the typical characteristics of fusion in live cells. Complementary lipopeptides were incorporated into liposomes and lead to their docking, then via the stalk intermediate to complete membrane fusion. As with SNARE protein mediated fusion, molecular recognition occurs through coiled-coil binding, without fusion caused by aspecific peptide-lipid interactions. The coiled-coil formation lead to the rapid membrane mixing of all initial liposomes, and the effects of lipopeptide and lipid concentrations on this process were studied.The combination of experimentally mapping the rate and route of liposome fusion under different conditions and the docking and fusion rates provided by a theoretical model gives a detailed understanding of the capacity of the reduced SNARE model to fuse liposome membranes. This understanding paves the way for future applications of the minimal model such as controlled nanoreactor mixing and the directed delivery of drugs to cells.

Together with Prof. Ravoo (Muenster University), we developed a novel system for the immobilization of liposomes and the formation of supported bilayers by using a coiled-coil binding motif which was patterned using microcontact printing-induced click chemistry. It was possible to obtain well defined structures of liposomes and supported bilayers. Furthermore a stimulus responsive supramolecular assembly consisting of cyclodextrin vesicles and adamantane modified oligopeptides was constructed. The system features the careful orchestration of several bioorthogonal noncovalent interactions.

The Kros group is also active in the field of biomaterials. For example we developed injectable hydrogels for in vivo delivery of proteins and hydrophobic drugs which were evaluated in zebrafish together with Spaink lab. After a visit to the Zink lab (UCLA), Kros started to work in the field of mesoporous silica nanoparticles which are also used for in vivo drug delivery. Recent funding initiated our efforts to use gold nanorods for single protein tracking in live cells. For these projects I collaborate with research groups from various disciplines, biology, physics and medicine.

The following projects are currently ongoing in the Kros lab:
-Membrane fusion, understanding the mechanism
-Light induced membrane fusion
-Fusion of liposomes with live cells and zebrafish embryos
-Giant Unilamellar Vesicles (GUV) as nanoreactors
-Artificial cells
-Biomineralization, controlled by peptides
-Hydrogels for drug delivery
-Mesoporous silica nanoparticles for drug delivery
-Tracking of a single protein inside a live cell
-Peptide amphiphile nanoparticles for vaccine delivery
-Directed formation of bloodvessels in 3D-hydrogels for tissue engineering

For these projects we are always looking for BSc and MSc students; we can always shape your internship to your interests. Whether you would like to do a supramolecular, organic synthesis, physical chemistry, chemical biology or interdisciplinary project, we will design a project that fits best with your interest. Please contact Dr. Alexander Kros for more information or an appointment; a.kros@chem.leidenuniv.nl

02/12/2016