Computational Modeling of Vesicle-Mediated Cell Transport

真核细胞特别重要的特征是其膜解剖的巨大复杂性和运输过程的高度组织化。囊泡被精确地传递到不同的细胞内和细胞外目的地的方式可以通过大量的例子来说明，例如神经递质被释放到神经细胞的突触前区域，胰岛素被输出到细胞表面。本项目的关键思想是将生物医学研究和机械数学模型的结果与高效的工程软件包相结合，以便模拟这种类型的过程，特别是囊泡的运输。这一结果将架起理论研究和医学实践之间的桥梁，并转变理解和治疗不同疾病的范式，这肯定是该项目的主要和长期目标。单独的目标与对囊泡运输的单一方面的模拟相吻合，即模拟囊泡形成、找到正确的目的地、与细胞器融合和运送其货物的机制。为此目的设想了几种不同方法的应用，但有三种主要策略构建了基本框架：脂质双层膜理论、均质化方法和扩散理论。这些方法将进一步与有限元、多尺度有限元等现代数值方法相结合，在最后阶段，单目标的实现将允许将囊泡运输模拟为一个连续的过程，并研究各种因素对整个过程的影响。通过这种方式，该项目将产生重大转变，从与单个细胞隔间和活动的子步骤相关的“静态”生物计算，转向对真实生命过程的“动态”模拟。

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.