Wound healing is a complex biological process that restores the integrity and strength of the skin. Keratinocytes and fibroblasts play pivotal roles in tissue repair through their interactions and signaling pathways. Keratinocytes proliferate to re-epithelialize the wound, while fibroblasts contribute to the formation of new extracellular matrix. Although cell proliferation is essential for wound healing, excessive proliferation can lead to scar formation. Therefore, strategies that balance proliferation and migration, along with proper mechanotransduction, are crucial for efficient wound repair. Sheep and camel milk contain numerous bioactive substances, such as insulin, lactoferrin, proline, and conjugated linoleic acid, that have demonstrated promising effects on wound healing. While direct evidence on skin cell proliferation and migration is limited, the properties of these bioactive substances suggest beneficial effects in these areas. Therefore, incorporating these milks into hydrogel dressings can promote wound healing. Moreover, improving the cell-material mechano-interaction in such hydrogels could lead to the development of novel regenerative medical therapies.

The myelin sheath is a multilayered glial membrane that surrounds axons providing insulation and rapid propagation of action potentials and contributing to structural support in both the central nervous system (CNS) and the peripheral nervous system (PNS). Therefore, myelin formation plays a crucial role in maintaining the integrity, connectivity, and functionality of the nervous system, as well as neuronal regeneration after injury or damage. Myelination in early developmental stages requires the molecular and mechanical exogenous cues provided mainly by the axons of the neurons, coupling the myelin-generating oligodendrocytes in the CNS and Schwann cells in the PNS. Complementary to early development, adaptive myelination dynamically regulates myelin remodeling in response to neuronal activity, ensuring optimal synaptic function and plasticity. Adaptive myelination is shown to be extremely mechanosensitive, requiring strict spatial constraints, stiffness, and topography for cell plasticity and myelination. Consequently, myelin regeneration is limited after traumatic injury and in demyelinating neurodegenerative diseases such as multiple sclerosis (MS). In addition to the inflammatory niche created around damaged myelin sheath, it is often overlooked that altered mechanical properties of the surrounding tissue are also pivotal in the inhibition of remyelination.This review focuses on the effects of mechanical cues on the polarization and plasticity of myelin generating cells, as well as on the induction of the myelin sheath during normal development and in pathological conditions. It also aims to give insights into potential mechanoepigenetic therapeutic approaches for demyelinating conditions.

Bone is a highly mechanosensitive tissue that adapts its function in response to mechanical cues. These cues are converted into biomechanical signals that regulate osteogenic gene expression through mechanotransduction. Bone homeostasis and the long-term bone adaptation to its mechanical environment depend on the proper integration of mechanical signals with transcriptional programs that regulate osteogenesis. Runt-related transcription factor 2 (RUNX2) is a pioneer transcription factor, a mechanosensitive molecule, which coordinates osteoblast differentiation and bone remodeling. RUNX2 activity in mechanically induced environments is subject to epigenetic regulation. Mechanical cues modulate RUNX2 through epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs. Proper epigenetic coordination ensures the stability of osteogenic gene expression. Any disruption of this mechanotransduction-epigenetic route leads to bone diseases such as osteoporosis, osteoarthritis, and dysfunctional fracture repair. Moreover, epigenetic reprogramming of RUNX2 is increasingly evident in bone tumors, particularly osteosarcoma, where aberrant RUNX2 activity is associated with cell proliferation, tumor progression, survival, metastasis, and loss of differentiation. This chapter examines current evidence on RUNX2 epigenetic regulation in response to mechanical forces, discusses how its orchestration relates to bone disease and bone tumor development, and underscores potential therapeutic opportunities that arise from targeting specific epigenetic mechanisms.

Development of cellular mechanisms to facilitate mechanosensing and mechanotransduction occurred very early in evolution during adaptation to the boundary conditions of Earth, in particular, gravity. Subsequently, with the evolution of increasingly complex organisms leading to Homo sapiens, multiple levels of biological regulatory control of mechanical loading were introduced for connective tissues of the musculoskeletal system. Integration of mechanosensing mechanisms with biological regulatory variables exhibits tissue-specific, lifespan-specific, sex specific features. A key integration component is the regulation of response to ground reaction forces. This chapter will discuss various features of this integration and its dynamic nature across the lifespan, and the critical role of the cell-extracellular matrix relationship, and how sex-specific variables appear to influence the functioning of connective tissues, particularly in females, where lifespan transitions (i.e., puberty, pregnancy and lactation, and menopause) appear to contribute to tissue responses to loading.

Cells have a mechanism that converts physical forces into biochemical signals, a critical process known as "mechanotransduction." Mechanotransduction plays a vital role in regulating multiple developmental and homeostatic events, including skeletal formation. Although underappreciated for decades, accumulated evidence now suggests that primary cilia play an important role in transducing mechanical stimuli. Since defects in the cilia result in multiple skeletal diseases, the importance of understanding the mechanisms between the mechanotransductive role of the cilia and skeletal health is paramount. However, the cellular mechanism of how cilia function as mechanosensors to control skeletal growth and homeostasis remains unclear. In addition, little is known about whether the manipulation of ciliary signaling related to defective mechanotransduction improves the skeletal disease conditions seen in osteoarthritis and osteoporosis. In this chapter, we provide a comprehensive overview of cilia and their role in mechanotransduction during skeletal development, with a focus on the function of key ciliary genes and intracellular signaling pathways in different skeletal cell types. We also highlight the broad impact of ciliary defects on mechanical stress-related skeletal diseases.

The role of, perhaps, the least understood biogenic amine, serotonin, goes beyond transmitting information within the neuroendocrine system. Serotonin has emerged as a critical factor in diverse signaling events across various organs and tissues. In the central nervous system, serotonin, also referred to by its chemical name 5-hydroxytryptamine, regulates behavior, mood, anxiety, sleep, and learning. In the periphery, serotonin signaling is a critical factor in gastrointestinal homeostasis, platelet activation, mammary gland development, lactation, and involution. Various aspects of mammary and gut physiology depend on related functions, where mechanical and biochemical signals converge. In this chapter, we explore some of the overlapping mechanosensory functions modulated by serotonergic signaling that characterize the relatively static mammary gland and the mechanical active gastrointestinal system in their physiologic and disease states.

For most eukaryotes, sexual reproduction depends on meiosis, a specialized cell division and differentiation program that halves the parental genome to produce gametes such as eggs, sperm, and pollen. Accurate segregation of homologous chromosomes during meiosis and the subsequent maturation of gametes are essential for reproductive success. Growing evidence suggests that mechanical forces acting on meiotic nuclei play essential roles in the development of healthy gametes. Here, we highlight how mechanical forces participate in key events through gamete development by focusing on three distinct yet related processes over space and time during the protracted meiotic prophase: (1) dynamic chromosome reorganization in early prophase, (2) control of gamete quality, and (3) gamete maturation. We center this chapter on Caenorhabditis elegans, in which the molecular logic of nuclear mechanotransduction during gamete development is especially well resolved. Where relevant, we summarize key findings in other model organisms to underscore conserved and divergent mechanisms. In addition to synthesizing current knowledge, this chapter outlines challenges and opportunities in studying the mechanisms and roles of force transmission and sensation at the nuclear envelope during gamete development-an emerging area with the potential to inform strategies that would improve reproductive health.

As the largest and stiffest cellular organelle, the nucleus is continuously under the influence of mechanical forces from external and internal sources. These forces trigger an adaptive response at the nuclear level that include changes in nucleocytoplasmic transport, chromatin architecture, or transcriptional activity, ultimately driving cell proliferation or differentiation. In preparation for mitosis, nuclear structure and organization is modified to ensure that chromosomes are efficiently captured and correctly separated. How these modifications impact the mechanical response of the nucleus remains a largely unexplored area. One emerging concept is that changes in the mechanical properties of the nucleus during early mitosis are required to ensure the timing and accuracy of chromosome segregation. This review will discuss the contribution of key nuclear components to nuclear mechanics and their relevance for chromosome segregation fidelity.

This chapter elucidates the fundamental role of magneto-mechanical stresses as a primary mechanism through which static and low-frequency magnetic fields influence cellular processes. We demonstrate that magnetic forces, particularly when amplified by magnetic nanoparticles (MNPs), exert precise control over cellular mechanics. At the membrane level, these forces induce subtle deformations that directly modulate the gating of mechanosensitive ion channels, such as Piezo1, thereby regulating Ca[2+] and K[+] fluxes and initiating downstream signaling cascades that govern gene expression, metabolism, and cytoskeletal remodeling. At higher force thresholds, magneto-mechanical stress triggers significant structural alterations, including membrane blebbing due to cortical detachment, which can act as a precursor to apoptosis-an effect with pronounced implications for cancer therapeutics. Furthermore, these magnetic stresses are transmitted through the cytoskeletal network, altering the tension in F-actin, microtubules, and intermediate filaments to remodel cell shape, motility, and adhesion, thereby influencing critical processes like cell migration and differentiation. We demonstrate that the noninvasive and selective nature of this magneto-mechanical approach offers a highly versatile and potent strategy for biomedical applications.

Mechanical forces are known to influence many cellular and extracellular processes in the body via mechanical signal transduction pathways, collectively called mechanotransduction. The corresponding mechanical information transmission is a multiscale process: starting at the nanoscale level of motor proteins, mechanical forces percolate through the cytoskeleton of the cell to create contractile forces in the extracellular matrix, where they are further transmitted to reach the tissue and organ levels. This force transmission is supported by various networks of simpler elements, such as collagen and elastin molecules that form fibrils, fibers, and fiber networks. The efficiency of force transmission, including the magnitude and direction of the force, heavily depends on the organization of the network structure. In the limit, when the transmission pathway through a network is broken, the force signal does not reach its target, and no response can happen. Thus, mechanical force and stress transmission require a connected or percolating network. This chapter reviews how emergent network phenomena contribute to mechanotransduction at various length scales. Sufficiently realistic intra- and extracellular network models should eventually be able to help understand disease pathogenesis and progression, as well as drug effects, with potential for guiding clinical treatments.

Multicellular tissues are shaped and remodeled during development, organogenesis, wound healing, cancer, and regeneration, as well as during a broad range of diseases. Time-lapse sequences of tissue movements convey a wealth of information about the processes driving their self-assembly and mechanobiology. Here we present StrainMapperJ, a digital image correlation (DIC) tool and supporting macros for the widely used open-source image analysis package ImageJ. StrainMapperJ can produce a diverse set of graphics for mechanical data exploration. At its core, StrainMapperJ uses the ImageJ plugin bUnwarpJ to map deformations in one image to match a second. From these results, StrainMapperJ can generate 2D maps of mechanical strain in the image frame, principal engineering strain and orientation, area strains, synthetic movement trajectories, and vorticity. StrainMapperJ can generate a variety of graphical outputs for quantitative analysis that registers or maps mechanical information directly onto the source image sequence. Additionally, the algorithms used in StrainMapperJ can yield quantitative information from short time-lapse sequences, often only a few minutes in duration, reducing the need for long-term imaging. In addition to these macros, we provide guidance on preparing image datasets, troubleshooting the analysis pipeline, and interpreting StrainMapperJ-produced maps for hypothesis generation and testing.

Over the past decade, theoretical and experimental work in mechanobiology has become increasingly interdependent, with modeling now serving as an essential tool for interpreting experiments and guiding measurements. Cellular mechanosensation, the conversion of mechanical cues into biochemical signals, governs essential processes such as migration, polarization, lineage specification, and tissue homeostasis, and its dysregulation contributes to disease. Quantitative models of mechanosensation have been central to clarifying how cells detect and respond to force across multiple scales, from ion channels and molecular bonds to adhesions, cytoskeletal dynamics, nuclear deformation, and transcriptional regulators such as YAP/TAZ (Yes-associated protein and transcriptional coactivator with PDZ-binding motif). In this chapter, we survey both experimental and theoretical advances in mechanosensation, emphasizing how mathematical and computational models complement experiments, expose limitations, and generate testable hypotheses and conceptual frameworks.

Podosomes are specialized, highly dynamic adhesion structures protruding from the membrane of animal cells. Their complex ultrastructure enables interactions with the microenvironment and extracellular matrix and the sensory and mechano-effector functions. Although historically attributed to monocytes, macrophages, and dendric cells, podosomes also occur in osteoclasts, endothelial cells, muscle, neural, cancer, and other cell types. This review describes podosome structure and podosomes' role in mechanotransduction and beyond.

As a professional mechanosensor, PIEZO1 converts mechanical stimuli-such as substrate stiffness, fluid shear stress, and membrane tension-into intracellular calcium influx, which in turn regulates a wide array of immune processes. The chapter details its significance across both innate and adaptive immunity, including T cell activation and migration, macrophage polarization, dendritic cell activation, natural killer cell cytotoxicity, neutrophil extracellular trap (NET) formation, and B cell antigen discrimination and class-switching to IgA. PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming. Despite these advances, key questions remain regarding its role in chronic disease, autoimmunity, and cancer immunity. Targeting PIEZO1 presents a promising therapeutic strategy for conditions driven by mechanical stress and immune dysfunction, such as fibrosis, atherosclerosis, and solid tumours, potentially inaugurating a new era of mechano-immunotherapy.

Understanding the mechanotransduction mechanisms underlying the tactile dimension of skin aging remains an underexplored aspect of dermatological and neurosciences. This investigation introduces a novel mechanosensory responsiveness index, tactile acuity index (TAI), derived from a time-frequency analysis of friction-induced vibrations recorded during controlled touch interactions utilizing the wearable tactile acquisition device (WTAD). By decomposing tactile signals across frequency bands specific to Merkel, Meissner, Ruffini, and Pacinian mechanoreceptors, TAI quantifies both the amplitude and spectral organization of vibrational energy transmitted through the skin.In a first experimental phase, TAI exhibited a clear monotonic decline across seven grades of paper textures, confirming that smoother surfaces produce weaker and spectrally narrower mechanical stimulation, thereby reducing mechanoreceptor recruitment. The strongest correlations were observed for Ruffini (R[2] = 0.89) and Pacinian (R[2] = 0.95) receptors, reflecting their sensitivity to macroscopic strain and high-frequency vibration. In an ensuing aging study involving 40 women aged 20-65, TAI revealed a pronounced reduction in mechanosensory activity across all receptor types, with the largest declines in deep mechanotransductive pathways. The associated time-frequency spectrograms further highlighted shorter, lower-amplitude bursts and restricted spectral bandwidths in older skin, indicating a progressive simplification of tactile encoding with age.Together, these findings validate TAI as a quantitative biomarker of tactile vitality, capable of distinguishing between textural and biological sources of sensory decline. By providing receptor-specific insights into mechanotransduction efficiency, this approach establishes a novel framework for diagnosing, monitoring, and potentially restoring tactile function through targeted cosmetic or therapeutic interventions.