Multiscale modeling of the neuromuscular system: Coupling neurophysiology and skeletal muscle mechanics.

Mathematical models and computer simulations have the great potential to substantially increase our understanding of the biophysical behavior of the neuromuscular system. This, however, requires detailed multiscale, and multiphysics models. Once validated, such models allow systematic in silico investigations that are not necessarily feasible within experiments and, therefore, have the ability to provide valuable insights into the complex interrelations within the healthy system and for pathological conditions. Most of the existing models focus on individual parts of the neuromuscular system and do not consider the neuromuscular system as an integrated physiological system. Hence, the aim of this advanced review is to facilitate the prospective development of detailed biophysical models of the entire neuromuscular system. For this purpose, this review is subdivided into three parts. The first part introduces the key anatomical and physiological aspects of the healthy neuromuscular system necessary for modeling the neuromuscular system. The second part provides an overview on state-of-the-art modeling approaches representing all major components of the neuromuscular system on different time and length scales. Within the last part, a specific multiscale neuromuscular system model is introduced. The integrated system model combines existing models of the motor neuron pool, of the sensory system and of a multiscale model describing the mechanical behavior of skeletal muscles. Since many sub-models are based on strictly biophysical modeling approaches, it closely represents the underlying physiological system and thus could be employed as starting point for further improvements and future developments. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models.