Biochemical reactions in a living cell are spatially restricted in compartments like the cytosol, nucleus, endoplasmic reticulum and mitochondria. The focus of our research is on mitochondria, which are micrometer-sized intracellular “reaction vessels” that host various biochemical reactions. Mitochondrial bioreactions are at the center of sustaining the function and viability of cells, tissues and organisms. The structure of mitochondria consists of an inner membrane surrounded by an outer membrane, with a space in between designated as the mitochondrial inter membrane space. The inner membrane contains many matrix-protruding folds (cristae) which enlarge its surface area and create a matrix compartment with a highly complex internal nanostructure. This sum-micrometer nanostructure has implications for the functionality of the mitochondria, as it contains membranes with specific functions but also constitutes a barrier for diffusion of biomolecules within the mitochondria . In general, the relationships between function and mitochondrial structure is not very well understood. With common biotechnology, it is difficult to generate variations of mitochondrial structure to study the biochemistry within. However, it is envisioned that the sub-micron structures of real mitochondria can be created in many design variations with state of the art nanofabrication technology. This is why, in a joint effort of Radboud UMC and UT, we are aiming at the development of nanofabricated artificial mitochondria as a platform to investigate the morphology-functionality relationship of real-life mitochondria.
The goal of the assignment is to first develop a library of biologically relevant nanostructures that could be of interest for studying the effect of morphology on biomolecular behavior. Next, a suitable fabrication process (or several alternatives) needs to be developed, based on lithography and thin film deposition and etching processes. Lithographic design and a process flow will be developed, and the process(es) will be executed. The behavior of biololecules (mainly diffusion) within the nanostructures will be performed at Radboud UMC, and results will be interpreted on the basis of an existing model , possibly with adaptations to make it more suitable for the new structures.
- C.E. Dieteren, S.C. Gielen, L.G. Nijtmans, J.A. Smeitink, H.G. Swarts, R. Brock, P.H. Willems, W.J.K. Koopman (2011) Solute diffusion is hindered in the mitochondrial matrix, Proc. Natl. Acad. Sci. USA 108, 8657-8662; https://doi.org/10.1073/pnas.1017581108
Han Gardeniers; Email: firstname.lastname@example.org