Development of a three-dimensional model of structural and functional changes during skeletal muscle growth: Experiment, simulation and validation

在生长过程中，肌肉组织经历广泛的结构和机械变化。因此，肌肉力量的增加与三维肌肉几何形状和肌肉的材料行为的适应有关。整个生长过程在保持肌肉功能的同时发生。理解和模拟生长的基本条件是获得结构和机械变化。该项目的目的是开发和验证骨骼肌的生长模型。这一目标通过两个相互作用的步骤来确保，其特征在于实验和建模之间的紧密复杂性。第一个项目阶段是为简单结构的兔子模型开发一个生长模型。比目鱼基于实验，我们在10个不同的动物年龄（生命的第4和第20周之间）确定特定的肌肉参数。这项实验工作包括确定主动肌肉特性、被动组织行为、收缩过程中的肌肉变形、三维肌肉结构以及肌肉组织的免疫组织学分析。基于这些实验结果，将识别各种状态变量（例如，羽角、组织刚度、纤维类型）的生长动力学，其将用于随后的步骤中，以开发生长模型（用于肌肉、腱膜和肌腱组织）。模型验证发生在实验力和变形数据，已施加从动态肌肉收缩实验的所有肌肉年龄。在第二个项目阶段，将在更复杂的模型上验证增长模型。跖肌这种多羽状肌的特点是复杂的纤维结构与内部腱鞘以及不均匀的纤维类型分布相结合。本项目中计划的生长模型的成功开发和验证将以一种独特的方式加速有关骨骼肌生长行为的知识。结构变化和收缩特性的知识是深入了解肌肉形状变化和生长过程中的分化的关键要求。适当的生长模型允许研究肌肉内部的状态变量（例如内部压力、应力、纤维方向）以及它们在生长期间的变化。这可能会导致更好地理解生物力学关系。此外，生长模型的成功开发可能是回答开放的进化生物学问题的基础，如三维排列（肌肉在肌肉包中的组装）和四肢的生长。

During growth muscle tissue is subjected to extensive structural and mechanical changes. Thereby, the increase of muscle force is related to the adaptation of the three-dimensional muscle geometry and the material behaviour of the muscle. The whole growth process happens while retaining the muscle function. The essential condition for the understanding and the modelling of growth is the acquisition of the structural and mechanical changes. Aim of the project is the development and validation of a growth model for skeletal muscles. This aim is ensured by two interacting steps, that are characterised by a tight complexity between experiment and modelling. The first project phase deals with the development of a growth model for the simple structured rabbit m. soleus. Rooted on experiments, we identify at 10 different animal ages (between the 4th and the 20th week of life) specific muscle parameters. This experimental work comprises the determination of the active muscle characteristics, the passive tissue behaviour, the muscle deformation during contraction, the three-dimensional muscle architecture, as well as the immunohistologic analysis of the muscle tissue. Based on these experimental results, growth kinetics for various state variables (e.g. pennation angle, tissue stiffness, fibre typ) will be identified, which will be used in a subsequent step for the development of the growth models (for muscle, aponeuroses, and tendon tissue). The model validation occurs on experimental force and deformation data that have been imposed from dynamic muscle contraction experiments for all muscle ages. In a second project phase the growth model will be verified on the much more complex m. plantaris. This multi-pennate muscle is characterised by a complex fibre architecture combined with inner tendon sheaths as well as an inhomogeneous fibre type distribution. A successful development and validation of the growth models as planed in this project would accelerate the knowledge concerning the growth behaviour of skeletal muscles in a distinct way. The knowledge of structural changes and contractile characteristics is a crucial requirement for a deeper understanding of muscle shape changes and the differentiation during growth. An adequate growth model allows the studying of state variables inside the muscle (e.g. inner pressure, stresses, fibre orientation) as well as their change during growth. This could lead to a better understanding of biomechanical relations. Furthermore, the successful development of growth models could be a basis to answer open evolutionary-biological questions like the three-dimensional arrangement (assembly of muscles in muscle packages) and the growth of extremities.