# Tuning the Cell and Biological Tissue Environment through Magneto-Active Materials
## 3 Theoretical and Computational Frameworks for Mechanically Mediated Biological Processes
### Modelling Mechanical Effects on Nervous System Behaviour  
The last few decades have experienced an emergence in interest of the scientific community in modelling both mechanical and electrophysiological behaviours of the nervous system from cell to tissue scales. Among these works, it is worth highlighting studies that address the mechano-electrophysiological problem from two main views: alteration of physiological responses due to mechanical damage; and intrinsic coupling of electrophysiology and mechanics during action potential formation and propagation.  
The search for criteria to link mechanical variables and functional deficits presents important limitations from experimental approaches. Computational models offer not only the possibility of analysing the problem by means of stress, strain and other mechanical variables, but also to translate knowledge and hypotheses from animal models to humans [16]. These computational tools have been used to provide the quantitative evaluation of mechanical effects on spinal cord injury [52], on the central nervous system [53; 54; 55; 56] and on functional and cognitive deficits [2; 57]. One of the first models to describe, in a coupled manner, both mechanics and electrophysiology is due to [PERSON] et al. [58]. In this work, the authors analysed left shift dynamics of ionic channel resulting from trauma conditions. Other pioneering work is due to [PERSON] and [PERSON] [59] and focused on mild retraction of myelin due to stretch and crush injuries. These ideas were then taken by [PERSON] and co-authors and incorporated into 1D [60; 61] and 3D [62] finite element frameworks to explore the effects of mechanical deformation and strain rate on axonal electrophysiology. In addition, alternative 3D non-axisymmetric mechano-electrophysiological models have been proposed [63; 64; 65]. Finally, in a recent series of works, [PERSON] and co-authors have proposed novel mechanistic energy-based criteria to link mechanical effects directly to medium-term cognitive deficits [57] and alterations in the electrophysiological behaviour at tissue scale [2; 57].  
Moreover, interesting experimental observations on the electro-mechanical coupling in neuronal membrane have led to new paradigms in the conceptualisation of the action potential nature. In this regard, different numerical approaches have been proposed. [PERSON] and [PERSON] [66] related the variation of compressive electrostatic forces (arisen from electrical depolarisation) within the membrane to mechanical waves called action waves. [PERSON] and co-authors have developed, in a series of articles [67; 68; 69] new theories that conceive action potential as an electrical wave that triggers other processes such as pressure waves in the axoplasm or longitudinal and transverse waves in the membrane. Finally, [PERSON] et al. [70] developed a mechano-electrophysiological model for neuronal axons, where the electro-mechanical coupling is explained by flexoelectric effects. More information on this can be found in a recent review article by [PERSON] et al. [71].