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，肌肉组织会经历广泛的结构和力学变化。因此，肌肉力量的增加与肌肉三维几何形状的适应和肌肉的物质行为有关。整个生长过程是在保留肌肉功能的情况下进行的。理解增长和建立增长模型的必要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生长模型。这一目标是通过两个相互作用的步骤来实现的，这两个步骤的特点是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比目鱼肌开发一个生长模型。以实验为基础，我们在10个不同的动物年龄(在生命的第4周和第20周之间)识别特定的肌肉参数。这项实验工作包括主动肌肉特征的测定、被动组织行为、收缩过程中肌肉变形、肌肉三维构筑以及肌肉组织的免疫组织学分析。基于这些实验结果，将确定各种状态变量(例如羽状角、组织硬度、纤维类型)的生长动力学，这将被用于后续步骤的生长模型的开发(肌肉、腱膜和肌腱组织)。模型的验证发生在所有肌肉年龄的动态肌肉收缩实验中施加的实验力和变形数据上。在第二个项目阶段，生长模型将在复杂得多的足底微藻上得到验证。这种多羽状肌肉的特点是复杂的纤维结构与内腱鞘相结合，以及不均匀的纤维类型分布。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对骨骼肌生长行为的了解。对肌肉结构变化和收缩特性的了解是深入了解肌肉形态变化和生长分化的关键。一个适当的生长模型可以研究肌肉内部的状态变量(例如，内部压力、应力、纤维取向)以及它们在生长过程中的变化。这可能导致对生物力学关系的更好理解。此外，生长模型的成功开发可能是回答公开的进化生物学问题的基础，如三维排列(肌肉包中的肌肉组装)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.