## 2 Mechanotransduction  
The transduction of a mechanical force into biological signals is obtained through conformational changes in the \"mechanosensory molecules\" or gravoreceptors. These molecules are characterized by two ends: the first is able to strictly connect to many fixed structures, such as the cytoskeleton, anchorage blocks, or extracellular matrix, while the other end modifies its conformation under mechanical stimuli [32]. In the last decade a large number of molecules have been identified as mechanosensors. Some cell types have evolved singular structures, specialized in the response to gravity, such as otoliths in the hair cells of the vestibular system and statoliths in plants, both of which are involved in transducing the mechanical stimulus to a mechanosensitive protein generating the biological signal [33]. Additionally, touch and hearing depend on mechanical forces detected by specific receptors (sensory neurons) that are able to sense mechanical changes induced by touch pressure or tympan deformation, respectively. The hair cells of the inner ear possess classical cilia on their surfaces, which are deformed by acoustic wave acting on tympan membrane and endolymph. In the inner ear, two anatomic structures mediate the gravity sensing and final mechanotransduction: the utricle and saccule [34]. Linear acceleration and gravity are sensed through the shear forces produced by the otoconia on the stereocilia and produce the transduction of the gravity or acceleration signals reaching acoustic areas of the brain. In particular, movement of the cilia causes the opening of mechanosensitive cation channels, then an altered membrane potential of the hair cells and a release of several neurotransmitters send information to the brain. Although this system has been roughly described, the molecules involved in this cascade are still not well known, and more studies must be conducted in order to clarify all molecular details [33]. Additionally, the bone skeleton is able to respond to mechanical and gravity stimuli through the presence of dendritic processes in the canaliculi structures between different osteocytes, cells that represent the differentiated stage of osteoblast [35]. Osteoblast activity is chiefly responsible for bone formation. Moreover, osteoclasts, a bone-specific form of macrophage, seem to be able to sense mechanical stimuli and play a role in mechanotransduction that is involved in bone maintenance through signals producing bone resorption [36]. It is still unclear what molecules actually generate the signal cascade both in osteocytes and in osteoclasts. Osteocytes can communicate by several second messengers released in the canaliculi, such as nitric oxide (NO), ATP, prostaglandandins, and Ca\({}^{2+}\)[37; 38; 39; 40]. Osteoclasts express integrins interacting with the extracellular matrix (ECM)/mineral matrix molecules and a proton pump acidifying the microenvironment defined by integrins adhesion (Figure 1). Strictly connected to the bone, skeletal muscle tissue is susceptible to mechanical input and is able to respond to the mechanical stretch. In fact, these stimuli can modulate a differentiation or proliferation of the muscle cells [41; 42]. Endothelial cells, bound to the blood vessels, are exposed to the blood flow that causes a shear stress on the cells [32]. Differences in the blood flow can alter the shear stress regulating a different gene expression profile in endothelial cells that can result in pathologic conditions like atherosclerosis. In this context, PECAM-1, a mechanosensory molecule tightly connected with cytoskeleton, vimentin, and actomyosin, in shear stress conditions, activates the Src family of kinase [43]. Under these same conditions, platelet can be activated following a perturbation of blood shear stress in the lumen of blood vessels [44]. Mechanical forces on the surface of the cells cause deformations in cellular structure causing changes in protein-protein interaction or in enzymatic activity.