# Tuning the Cell and Biological Tissue Environment through Magneto-Active Materials
## 2 Mechanically Mediated Biological Processes
### Mechanical Effects on Nervous System Behaviour  
Unlike other types of tissue, brain cell mechanical properties are not as clearly understood and are much more difficult to study and generalize [9; 10]. The number of physical and chemical variables, external and internal factors, as well as structure, creates complicated loops that make it hard to distinguish cause from effect. However, outstanding  
Figure 1: Examples of biological cells and tissue, whose functional response greatly depends on mechanical effects: (**A**) mechano-electrophysiological response in brain tissue, experimental (adapted with permission from [1]) (left) and modelling (adapted with permission from [2]) (right) insights; (**B**) bone adaptation to mechanical loading, experimental (adapted with permission from [3]) (left) and modelling (adapted with permission from [4]) (right) insights; (**C**) cancer cell proliferation and migration depending on mechanical properties of the substrate, experimental (adapted with permission from [5]) (left) and modelling (adapted with permission from [6]) (right) insights; (**D**) durotaxis in epithelial cell migration depending on mechanical properties of the substrate, experimental (adapted with permission from [7]) (left) and modelling (adapted with permission from [8]) (right) insights. progress has been made in deciphering and using the mechano-properties as indicators of problems. The central nervous system is mainly comprised of neurons supported by glial cells and display the behaviour of elastic solids [11]. However, this interpretation is often debated, as glial cells present significantly softer characteristics than the cells they support. Some glial cells are twice as soft as neurons and present lower elastic storage modulus and viscous loss modulus. Experiments have determined that these cells' functions resemble more of a cushioning system or flexible embedding than a scaffold, protecting neurons from mechanical trauma, displaying very elastic properties [12]. The cells themselves are tightly held in place by cerebrospinal fluid. This in turn also applies pressure over the nervous system, which can increase considerably in the case of trauma. Although elastic behaviour dominates over viscous behaviour across the nervous systems, properties differ due to the varying distribution of organelles. Many efforts have been made in identifying causes for medical complications in patients of traumatic incidents. Understanding the specific triggers and mechanisms behind traumatic brain damage and its development into neurodegenerative and neuropsychiatric disorders is an ongoing challenge. In the case of external trauma, pathologies are thought to be mechanically initiated and to result in many interconnected variables and processes. Some properties, such as shear deformation energy, which naturally varies during the lifecycle of the cell/tissue may be used as an indicator of trauma. The associated damage at the axonal or tissue scale, especially relevant at high deformation rates, can result into electrophysiological alterations and, following this, loss of sensory and motor function [2; 13]. Damageable mechanical conditions are likely to occur during loading scenarios, such as sport activities, falls, and car accidents [14], or during even more dangerous scenarios such as blast loading (e.g., explosions) [15]. Therefore, the identification of clear links between mechanics and functional and cognitive deficits is of great interest. To this end, different criteria have been proposed to identify and predict such physiological alterations due to mechanical effects (i.e., axonal stretch, deformation energy, deformation energy rate) [1; 2; 16; 17]. In the same way that chemical changes affect the properties of the system, mechanical processes affect the final chemical properties, causing a feedback loop. This two-way effect is most evident in signalling, as the capacity for generating action potentials can be affected by trauma.