Computational Modeling of Vesicle-Mediated Cell Transport

真核细胞特别重要的特征是其膜解剖结构的巨大复杂性和运输过程的高水平组织。通过许多例子，如神经递质释放到神经细胞的突触前区域和胰岛素输出到细胞表面，可以说明囊泡到达细胞内和细胞外目的地的精确路线。本项目的关键思想是将生物医学研究和力学数学模型的结果与高效的工程软件包结合起来，以模拟这种类型的过程，特别是囊泡运输。研究结果应在理论研究和医学实践之间架起桥梁，改变人们对不同疾病的认识和治疗模式，这当然是该项目的首要和长期目标。单个目标与囊泡运输的单个方面的建模相一致，即与囊泡形成，找到正确的目的地，与细胞器融合并运送货物的机制的模拟。为此目的设想了几种不同方法的应用，但三种主要策略构建了基础骨架：脂质双层膜理论、均质化方法和扩散理论。上述方法将进一步与现代数值技术，如有限元法和多尺度有限元法相结合。在最后阶段，单个目标的实现将允许将囊泡运输作为一个连续过程进行模拟，并研究各种因素对整个过程的影响。这样，该项目将产生一个重大的转变，从“静态”的生物计算与单细胞区隔及其活动的子步骤相关，到“动态”模拟真实的生活过程。

The particularly 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 the present 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 should bridge the theoretical investigations and medical praxis and shift the paradigm in understanding and remedying different diseases, which certainly is the primary and long-term goal of the project. The individual 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. 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.