Search Results (242)

The extracellular matrix (ECM) is a dynamic, tissue-specific network that integrates biochemical and mechanical cues to regulate cell behavior and organ homeostasis. Increasing evidence indicates that dysregulated ECM remodeling is an upstream driver of chronic human diseases rather than a passive consequence of injury. This review summarizes principles of ECM organization, mechanotransduction, and pathological remodeling and highlights translational opportunities for ECM-targeted therapies, biomaterial platforms, and precision diagnostics. We conducted a narrative synthesis of foundational and recent literature covering ECM composition and turnover, stiffness-dependent signaling, and disease-associated remodeling across fibrosis/cardiovascular disease, cancer, and metabolic disorders, together with advances in ECM-based biomaterials, drug delivery, and ECMderived biomarkers and imaging. Across organs, a self-reinforcing cycle of altered matrix composition, excessive crosslinking, and stiffness-dependent mechanotransduction (including integrin–FAK and YAP/TAZ pathways) sustains fibroinflammation, myofibroblast persistence, and progressive tissue dysfunction. In tumors, aligned and crosslinked ECM promotes invasion, immune evasion, and therapy resistance while also shaping perfusion and drug penetration. Translational strategies increasingly focus on modulating ECM synthesis and crosslinking, normalizing rather than ablating matrix architecture, and targeting ECM–cell signaling axes in combination with anti-fibrotic, cytotoxic, or immunotherapeutic regimens. ECM biology provides a unifying framework linking pathogenesis, therapy, and precision diagnostics across chronic diseases. Clinical translation will benefit from standardized quantitative measures of matrix remodeling, mechanism-based biomarkers of ECM turnover, and integrative imaging–omics approaches for patient stratification and treatment monitoring. Full article

Neuromechanobiology has emerged as a multidisciplinary field at the interface of neuroscience and mechanobiology, aiming to elucidate how mechanical forces influence the development, organization, and function of the nervous system. This review offers a comprehensive overview of the historical evolution of the discipline, its molecular and biophysical foundations, and the experimental strategies employed to investigate it. Recent advances have revealed the pivotal roles of substrate stiffness, mechanical signaling, and force transduction in neural stem proliferation, axon guidance, synapse formation, and neural circuit maturation. All these effects originate at the molecular level and extend to the mesoscopic scale. Disrupted mechanotransduction has been increasingly implicated in neurodevelopmental disorders and neurodegenerative diseases, underscoring its clinical relevance. Key unresolved questions and future directions are also highlighted, with emphasis on the need for integrative approaches to decipher the complex interplay between mechanical forces and neural function. Full article

Obesity is increasingly recognized not only as a metabolic disorder but also as a condition marked by the structural and functional deterioration of skeletal muscle and tendon tissues. Central to this process is the dysregulation of the extracellular matrix (ECM) resulting in fibrosis and ectopic fat accumulation, factors that contribute to impaired tissue mechanics. Myostatin (GDF-8), a member of the TGF-β superfamily, is known as a negative regulator of muscle mass. It can also mediate interaction between adipose and other tissues including muscles and tendons. In obesity, elevated myostatin levels have been reported to be associated with insulin resistance, muscle atrophy, and activation of SMAD2/3 signaling, while experimental and preclinical studies indicate that myostatin inhibition can improve glucose homeostasis and increase lean mass. Emerging evidence suggests that myostatin also plays a critical role in muscle ECM and tendon remodeling. Restoring its physiological levels may help reverse ECM disorganization and reduce tissue fragility associated with musculotendinous dysfunction. This review highlights the multifaceted role of myostatin in obesity, beyond its role in muscle catabolism, to include modulation of structural integrity, metabolism, and mechanical adaptability of the musculotendinous system. Understanding how myostatin responds to metabolic stress and affects biomechanical remodeling offers novel insights into obesity-related muscle and tendon dysfunction. Full article

The brain’s extracellular matrix (ECM) serves as a dynamic and instructive regulator of glioma progression. The ECM provides structural support while integrating pharmacological and mechanical signals that influence glioma initiation, progression, and treatment resistance. Deviant ECM remodeling fosters tumor heterogeneity, invasion, and immune evasion by altering stiffness, composition, and cellular matrix signaling. We proposed that ECM remodeling in gliomas not only facilitates tumor growth and heterogeneity but also establishes advantageous biophysical and metabolic conditions that foster treatment resistance and recurrence. Our objective is to analyze current findings regarding the structural, biochemical, and mechanical roles of the brain ECM in glioma growth, emphasizing its contribution to tumor heterogeneity, mechanotransduction, immunological modulation, and its potential as a therapeutic target. Method: A comprehensive literature review was conducted using scientific databases including PubMed, Web of Science, and Scopus. Peer-reviewed literature published between 2000 and 2025 was selected for its relevance to ECM composition, stiffness, remodeling enzymes, extracellular vesicles, and mechanobiological processes in gliomas. Results: Recent investigations demonstrate that glioma cells actively alter the ECM by secreting collagens, laminins, and metalloproteinases, establishing a feedback loop that facilitates invasion and resistance. Discussion: Mechanical variables, such as ECM stiffness and solid stress, influence glioma growth, metabolism, and immune exclusion. Moreover, extracellular vesicles facilitate significant extracellular matrix remodeling and improve communication between tumors and stromal cells. The disruption of ependymal and subventricular extracellular matrix niches enhances invasion and cerebrospinal fluid-mediated signaling. The remodeling of the ECM influences glioma growth through interconnected biochemical, mechanical, and immunological mechanisms. Examining ECM stiffness, crosslinking enzymes, and vesicle-mediated signaling represents a potential therapeutic approach. Integrative methodologies that combine mechanobiology, imaging, and multiomics analysis could uncover ECM-related vulnerabilities to improve glioma treatment. Full article

Cancer progression is driven not only by biochemical signals but also by abnormal physical forces within a stiffened tumor microenvironment. This review re-examines the anticancer compound sulforaphane (SFN) through the integrative lens of tumor biomechanics. We propose SFN functions as a “mechano-modulator,” whose pleiotropic effects converge to disrupt pro-invasive mechanotransduction. SFN targets key force-sensitive pathways (e.g., YAP/TEAD, Rho/ROCK), destabilizes invasion machinery (cytoskeleton, invadopodia), and promotes tissue-level changes such as extracellular matrix remodeling. While preclinical evidence for this mechano-modulatory role is compelling, this perspective also highlights the critical need for clinical validation and discusses the key translational challenges. By systematically linking SFN’s molecular actions to the biophysics of tumor progression, this synthesis provides a novel framework for understanding its efficacy and outlines a rational path for its future development as a mechano-inspired therapeutic. Full article

Background: Mechanical loading is a fundamental regulator of bone remodelling; however, the mechanotransduction mechanisms governing alveolar bone adaptation under tensile-dominant orthodontic loading remain insufficiently defined. In particular, the molecular pathways associated with tension-driven cortical modelling in the periodontal ligament (PDL)–bone complex have not been systematically interpreted in the context of advanced biomechanical simulations. Methods: A nonlinear finite element model of the alveolar bone–PDL–tooth complex was developed using patient-specific CBCT data. Three loading configurations were analysed: (i) conventional orthodontic loading, (ii) loading combined with corticotomy alone, and (iii) a translation-dominant configuration generated by the Bone Protection System (BPS). Pressure distribution, displacement vectors, and stress polarity within the PDL and cortical plate were quantified across different bone density conditions. The mechanical outputs were subsequently interpreted in relation to established mechanotransductive molecular pathways involved in osteogenesis and angiogenesis. Results: Conventional loading generated compression-dominant stress fields within the marginal PDL, frequently exceeding physiological thresholds and producing moment-driven root displacement. Corticotomy alone reduced local stiffness but did not substantially alter stress polarity. The BPS configuration redirected loads toward a tensile-favourable mechanical environment characterised by reduced peak compressive pressures and parallel (translation-dominant) displacement vectors. The predicted tensile stress distribution is compatible with activation profiles of key mechanosensitive pathways, including integrin–FAK signalling, Wnt/β-catenin–mediated osteogenic differentiation and HIF-1α/VEGF-driven angiogenic coupling, suggesting a microenvironment that may be more conducive to cortical apposition than to resorption. Conclusions: This study presents a computational–molecular framework linking finite element–derived tensile stress patterns with osteogenic and angiogenic signalling pathways relevant to alveolar bone remodelling. The findings suggestthat controlled redirection of orthodontic loading toward tensile domains may shift the mechanical environment of the PDL–bone complex toward conditions associated with osteogenic than resorptive responses providing a mechanistic basis for tension-induced cortical modelling. This mechanobiological paradigm advances the understanding of load-guided alveolar bone adaptation at both the tissue and molecular levels. Full article

The mammalian lung operates under a biological paradox, requiring architectural fragility for gas exchange while maintaining robust regenerative plasticity to withstand injury. The Hippo signaling pathway has emerged as a central “rheostat” in orchestrating these opposing needs, yet the distinct roles of its downstream effectors remain underappreciated. This review synthesizes recent genetic and mechanobiological advances to propose a “Tale of Two Effectors” model, arguing for the functional non-redundancy of YAP and TAZ. We posit that YAP functions to drive airway progenitor expansion, mechanical force generation, and maladaptive remodeling. Conversely, TAZ—regulated uniquely via transcriptional mechanisms and mechanotransduction—acts as an obligate driver of alveolar differentiation and adaptive repair through an NKX2-1 feed-forward loop. Furthermore, we introduce the “See-Saw” model of tissue fitness, where mesenchymal niche collapse releases the mechanical brake on the epithelium, triggering the bronchiolization characteristic of pulmonary fibrosis. Finally, we extend this framework to malignancy, illustrating how Small Cell Lung Cancer (SCLC) subtypes mirror these developmental and regenerative states. This integrated framework offers new therapeutic distinct targets for modulating tissue fitness and resolving fibrosis. Full article

Mechanical loading generated during physical activity and exercise is a fundamental determinant of musculoskeletal development, adaptation, and regeneration. Exercise-based mechanotherapy, encompassing structured movement, resistance training, stretching, and device-assisted loading, has evolved from empirical rehabilitation toward mechanism-driven and precision-oriented therapeutic strategies. At the macroscopic level, biomechanical principles governing load distribution, stress–strain relationships, and tissue-specific adaptation provide the physiological basis for exercise-induced tissue remodeling. At the molecular level, mechanical cues are transduced into biochemical signals through conserved mechanotransduction pathways, including integrin–FAK–RhoA/ROCK signaling, mechanosensitive ion channels such as Piezo, YAP/TAZ-mediated transcriptional regulation, and cytoskeleton–nucleoskeleton coupling. These mechanisms orchestrate extracellular matrix (ECM) remodeling, cellular metabolism, and regenerative responses across bone, cartilage, muscle, and tendon. Recent advances in mechanotherapy leverage these biological insights to promote musculoskeletal tissue repair and regeneration, while emerging engineering innovations, including mechanoresponsive biomaterials, 4D-printed dynamic scaffolds, and artificial intelligence-enabled wearable systems, enable mechanical loading to be quantified, programmable, and increasingly standardized for individualized application. Together, these developments position exercise-informed precision mechanotherapy as a central strategy for prescription-based regenerative rehabilitation and long-term musculoskeletal health. Full article

Cells sense and transmit mechanical forces exerted by their environment to the nucleus via adhesion sites and the cytoskeleton. The nucleus interprets these mechanical inputs and determines cell fate and behavior by regulating gene expression. This review addresses how force-generated signals at the cell–extracellular matrix (ECM) interface influence adhesion, signaling, nuclear function, and tissue remodeling. Disruption of these mechanotransduction pathways contributes to the development of diseases such as cancer, fibrosis, and cardiovascular disorders. Advances in technologies that enable the investigation of the underlying mechanisms will support the development of novel treatment strategies for such diseases. Full article

Mechanobiology plays a pivotal role in skeletal development and bone remodeling. Mechanical signals such as matrix stiffness, fluid shear stress, and hydrostatic pressure activate the Runt-related transcription factor 2 (RUNX2) bone-specific transcription factor through pathways including the mitogen-activated protein kinase (MAPK) signaling cascade and yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) effectors. RUNX2 itself affects chromatin remodeling and nuclear architecture via Lamin A/C and Nesprin 1, thereby directing osteogenic differentiation. Thus, RUNX2 acts both as a mechanosensor and mechanoregulator, whereas RUNX2’s mechanosensitivity has been leveraged as a target to achieve bone regeneration. Notably, post-translational modifications and epigenetic alterations can orchestrate this regulation, integrating metabolic and circadian signals. However, due to RUNX2’s nuclear localization, its targeting remains a challenging issue. To this end, indirect targeting, through mammalian/mechanistic target of rapamycin complex 1 (mTORC1) or microRNAs (miRNAs), offers new strategies to employ biomechanics in an attempt to intervene with bone diseases driven by mechanical cues or degeneration, and ultimately repair and regenerate the damaged tissues. Herein we critically elaborate upon molecular aspects of RUNX2 regulation towards exploitation at the clinical level. Full article

Sensory systems allow the detection of external and internal cues essential for adaptive responses. Chemosensation exemplifies this integration, guiding feeding, mating, and toxin avoidance while also influencing physiological regulation. Across taxa, chemical detection relies on diverse receptor families, and emerging evidence reveals that transient receptor potential (TRP) channels—traditionally associated with phototransduction, thermosensation, and mechanotransduction—also mediate chemosensory functions. Studies in Drosophila melanogaster and vertebrates demonstrate that TRPs detect tastants, odorants, and internal chemical states, highlighting their evolutionary conservation and functional versatility. This review synthesizes current insights into the roles of TRP channels across four major domains: taste, smell, internal state, and central circuit modulation. Using D. melanogaster and mammalian systems as comparative frameworks, we highlight how TRP channels function as polymodal sensors, signal amplifiers, and modulators embedded within canonical receptor pathways rather than as standalone chemoreceptors. Recognizing these integrative functions not only expands our understanding of how organisms coordinate behavior with internal states but also points to TRP channels as potential targets for addressing chemosensory disorders and metabolic diseases. This framework highlights key directions for future research into TRP-mediated sensory and homeostatic regulation. Full article

Despite extensive research on fascial mechanobiology, no unified mechanotransduction framework has been established to explain how mechanical forces translate into adaptive cellular responses in fascial tissue. This narrative review synthesizes evidence from mesenchymal cell and fibroblast research to propose the Ca²⁺–Hyaluronan (CHA) axis as a comprehensive mechanotransduction feedback loop for fascia phenomenology. The CHA framework describes how mechanical stress activates Ca²⁺ channels (Piezo1, TRPV4, P2Y2), triggering HAS2-mediated hyaluronan (HA) synthesis. The molecular weight of synthesized HA then determines receptor signaling outcomes: high-molecular-weight HA binds CD44 to promote tissue stability and quiescence, while low-molecular-weight HA fragments activate RHAMM to drive remodeling and repair—a dynamic oscillation termed “Quiet or Riot.” Three key conclusions emerge: First, the CHA framework is well supported by existing literature on mesenchymal cells, providing a testable model for fascial mechanobiology. Second, HA molecular weight dynamics and CD44/RHAMM oscillation have direct implications for optimizing movement, manual therapy, and rehabilitative interventions. Third, while HA-CD44/RHAMM signaling is broadly implicated in tissue remodeling, Ca²⁺-dependent regulatory mechanisms specific to fasciacytes require experimental validation. A critical translational gap remains: the absence of quantitative mechanical thresholds distinguishing beneficial from pathological loading limits clinical application. Future research should employ 3D matrix models, live imaging, receptor manipulation, and omics profiling to establish these thresholds and validate the CHA framework in fasciacytes. Understanding fascial mechanotransduction through the CHA loop may transform approaches to movement prescription, manual therapy, and treatment of fascial dysfunction. Full article

Cell motility—the dynamic process encompassing migration, adhesion modulation, cytoskeletal remodeling, and extracellular matrix (ECM) interactions—is fundamental to ocular homeostasis. In glaucoma, disrupted motility of trabecular meshwork (TM) and Schlemm’s canal (SC) cells contributes to impaired aqueous humor outflow and elevated intraocular pressure (IOP), while reactive motility of optic nerve head (ONH) glial cells promotes fibrosis and neurodegeneration. Mechanistically, TM/SC motility is regulated by Rho GTPase and ROCK signaling, focal adhesion dynamics, and ECM interactions, while glial cells respond to mechanical stress and cytokines such as TGF-β₂. Cytoskeletal alterations, ECM stiffening, and endothelial–mesenchymal transition (EndMT) contribute to glaucomatous damage by reducing normal cell motility and tissue remodeling capacity. Aberrant motility at the ONH, including heterogeneous astrocytic reactivity, leads to lamina cribrosa remodeling and retinal ganglion cell degeneration. Therapeutically, ROCK inhibitors improve TM/SC motility and outflow, suppress EndMT, and may confer neuroprotection. Stem cell-based strategies and modulation of TGF-β₂ or mechanotransduction pathways represent emerging approaches to restore physiological motility and regenerative potential. Despite promising advances, challenges remain in ensuring targeted, durable, and safe modulation of cellular dynamics. Understanding and therapeutically harnessing cell motility offers a unifying framework to address both pressure-dependent and neurodegenerative mechanisms in glaucoma. Full article

Collagen VI-related myopathies (COL6-RM) encompass a spectrum of disorders characterized by muscle weakness, joint contractures, and connective tissue abnormalities resulting from mutations in the collagen VI genes. While muscle pathology has been extensively studied, tendon dysfunction has emerged as a critical yet underexplored contributor to disease severity, particularly in the development of joint contractures. Tendons from patients and animal models show disrupted collagen fibrillogenesis, altered extracellular matrix (ECM) composition, and impaired cellular mechanotransduction. Various defects in ECM remodeling pathways further exacerbate tendon pathology. Importantly, current clinical management remains limited to orthopedic interventions with modest outcomes, and targeted pharmacological strategies or gene-editing therapies are not yet available for clinical application. Therefore, understanding the basic pathogenic mechanisms underlying tendon dysfunction is essential for identifying novel therapeutic targets. This review provides a comprehensive synthesis of current understanding and recent advances concerning the role of mutated collagen VI in cellular and molecular mechanisms underlying tendon dysfunction. Emphasis is placed on the role of mutated collagen VI in the modulation of key signaling pathways related to mechanotransduction and primary cilium function in COL6-RM. By discussing these multifaceted contributions to disease pathogenesis, this review outlines future research directions in the field and highlights potential pathways for targeted therapeutic interventions. Full article

Glycation-induced modifications of extracellular matrix (ECM) proteins, including collagen, are increasingly recognized as critical modulators of cellular behavior, particularly in pathophysiological contexts such as aging and diabetes. While their impact on general cell adhesion has been explored, the specific consequences for mesenchymal stem cell (MSC) mechanotransduction remain poorly defined. In this study, we investigated the temporal and mechanistic aspects of adhesion and mechanosensitive signaling in adipose-derived MSCs (ADMSCs) cultured on native versus glycated collagen substrates. Our findings identify two temporally distinct adhesion mechanisms: an initial pathway mediated by the receptor for advanced glycation end-products (RAGE), which is activated within the first 30 min following substrate engagement, and a later-stage adhesion process predominantly governed by integrins. Immunofluorescence analysis demonstrated maximal nuclear localization of YAP/TAZ transcriptional regulators during the initial adhesion phase, coinciding with RAGE engagement. This nuclear enrichment was progressively attenuated as integrin-mediated focal adhesions matured, suggesting a dynamic shift in receptor usage and mechanotransductive signaling. Interestingly, glycated collagen substrates accelerated early cell attachment but impaired focal adhesion maturation, suggesting a disruption in integrin engagement. Endogenous collagen synthesis was consistently detected at all examined time points (30 min, 2 h, and 5 h), suggesting a constitutive biosynthetic activity that remains sensitive to the glycation state of the substrate. Atomic force microscopy (AFM) demonstrated that glycation disrupts collagen fibrillogenesis: while native collagen forms a well-organized network of long, interconnected fibrils, GL-1 substrates (glycated for 1 day) displayed sparse and disordered fibrillary structures, whereas GL-5 substrates (5-day glycation) exhibited partial restoration of fibrillar organization. These matrix alterations were closely associated with changes in adhesion kinetics and mechanotransduction profiles. Taken together, our findings demonstrate that collagen glycation modulates both adhesion dynamics and mechanosensitive signaling of MSCs through a dual-receptor mechanism. These insights have significant implications for the design of regenerative therapies targeting aged or metabolically compromised tissues, where ECM glycation is prevalent. Full article