Computational Modeling of Vesicle-Mediated Cell Transport
Three (main) stages of the intracellular vesicle transport; graphics adapted from Olkkonen and Ikonen (2000).
Within the multiscale FEM the simulation of a material with a heterogeneous microstructure is split into two boundary-value problems.
One important characteristics of eukaryotic cells are the enormous complexity of their membrane anatomy and the high level of organization of the transport processes. The surprisingly precise manner of the routing of vesicles to various intracellular and extracellular destinations can be illustrated by numerous examples such as the release of neurotransmitters into the presynaptic region of a nerve cell and the export of insulin to the cell surface.
The key idea of this particular project is to couple results of biomedical investigations and mechano-mathematical models with the highly efficient engineering software packages in order to simulate this type of processes, in particular the vesicle transport. The results bridge the theoretical investigations and medical practice and shift the paradigm in understanding and remedying different diseases, which certainly is the primary and long-term goal of the project. The project objectives coincide with the modeling of single aspects of the vesicle transport, namely with the simulation of mechanisms by which the vesicles form, find their correct destination, fuse with organelles and deliver their cargo. The application of several different approaches is envisaged for this purpose, but three main strategies build the underlying skeleton: the theory of lipid bilayer membranes, the homogenization method and the diffusion theory. The mentioned approaches will furthermore be combined with the modern numerical techniques such as the finite element method and the multiscale finite element method.
In the final stage, the realization of single objectives will allow the simulation of vesicle transport as a continuous process and the study of the impact of various factors on the whole process. In this way, the project will yield a significant shift from "static" bio-computations related to the single cell compartments and substeps of its activities, to the "dynamic" simulation of the real living processes.
Funding: Austrian Science Fund (FWF)