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Computational Modeling of Vesicle-Mediated Cell Transport

囊泡介导的细胞运输的计算模型

基本信息

批准号：
385960030
负责人：
Professorin Dr.-Ing. Sandra Klinge
金额：
--
依托单位：
Institut für Biomechanik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/385960030?language=en
关键词：
Computational Modeling Vesicle Mediated Cell

项目摘要

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.

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。许多例子可以说明囊泡到各种细胞内和细胞外目的地的令人惊讶的精确方式，例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。数学模型与高效的工程软件包，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，并在理解和治疗不同疾病方面转变范式，这无疑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，即与囊泡形成的机制的模拟相一致，找到它们正确的目的地，与细胞器融合并运送它们的货物。几种不同的方法的应用设想为此目的，但三个主要的策略建立基本的骨架：脂质双层膜的理论，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，单一目标的实现将允许模拟囊泡运输作为一个连续的过程，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转变，从“静态”生物计算相关的单细胞隔间和子步骤的活动，“动态”模拟的真实的生活过程。