CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic models of the stretching biosensor propose equal roles for both anchoring domains. Using deletion mutants and domain replacements, we have analyzed the relative importance of the focal adhesion anchoring domains on CAS localization and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction. We confirmed the predicted prerequisite of the focal adhesion targeting for CAS-dependent mechanosensing and unraveled the critical importance of CAS SH3 domain in mechanosensing. We further show that CAS localizes to the force transduction layer of focal adhesions and that mechanical stress stabilizes CAS in focal adhesions.

• MeSH
• buněčná adheze MeSH
• buněčný převod mechanických signálů * MeSH
• fibroblasty cytologie   metabolismus   MeSH
• fokální adheze metabolismus   MeSH
• mechanický stres MeSH
• mutantní proteiny chemie   MeSH
• myši MeSH
• proteinové domény MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• signální transdukce MeSH
• stabilita proteinů MeSH
• substrátový protein asociovaný s Crk chemie   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Living cells are constantly exposed to mechanical stimuli arising from the surrounding extracellular matrix (ECM) or from neighboring cells. The intracellular molecular processes through which such physical cues are transformed into a biological response are collectively dubbed as mechanotransduction and are of fundamental importance to help the cell timely adapt to the continuous dynamic modifications of the microenvironment. Local changes in ECM composition and mechanics are driven by a feed forward interplay between the cell and the matrix itself, with the first depositing ECM proteins that in turn will impact on the surrounding cells. As such, these changes occur regularly during tissue development and are a hallmark of the pathologies of aging. Only lately, though, the importance of mechanical cues in controlling cell function (e.g., proliferation, differentiation, migration) has been acknowledged. Here we provide a critical review of the recent insights into the molecular basis of cellular mechanotransduction, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program. Specifically, by recapitulating the processes involved in the interpretation of ECM remodeling by Focal Adhesions at cell-matrix interphase, we revise the role of cytoskeleton tension as the second messenger of the mechanotransduction process and the action of mechano-responsive shuttling proteins converging on stage and cell-specific transcription factors. Finally, we give few paradigmatic examples highlighting the emerging role of malfunctions in cell mechanosensing apparatus in the onset and progression of pathologies.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

• MeSH
• bolest MeSH
• buněčný převod mechanických signálů * fyziologie   MeSH
• migréna * diagnóza   MeSH
• nocicepce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

• Publikační typ
• časopisecké články MeSH

Cells are continuously sensing their microenvironment and subsequently respond to different physicochemical cues by the activation or inhibition of different signaling pathways. To study a very complex cellular response, it is necessary to diminish background environmental influences and highlight the particular event. However, surface-driven nonspecific interactions of the abundant biomolecules from the environment influence the targeted cell response significantly. Yes-associated protein (YAP) translocation may serve as a marker of human hepatocellular carcinoma (Huh7) cell responses to the extracellular matrix and surface-mediated stresses. Here, we propose a platform of tunable functionable antifouling poly(carboxybetain) (pCB)-based brushes to achieve a molecularly clean background for studying arginine, glycine, and aspartic acid (RGD)-induced YAP-connected mechanotransduction. Using two different sets of RGD-functionalized zwitterionic antifouling coatings with varying compositions of the antifouling layer, a clear correlation of YAP distribution with RGD functionalization concentrations was observed. On the other hand, commonly used surface passivation by the oligo(ethylene glycol)-based self-assembled monolayer (SAM) shows no potential to induce dependency of the YAP distribution on RGD concentrations. The results indicate that the antifouling background is a crucial component of surface-based cellular response studies, and pCB-based zwitterionic antifouling brush architectures may serve as a potential next-generation easily functionable surface platform for the monitoring and quantification of cellular processes.

• MeSH
• akrylamidy chemie   MeSH
• biokompatibilní potahované materiály chemie   MeSH
• bioznečištění prevence a kontrola   MeSH
• buněčný převod mechanických signálů * MeSH
• extracelulární matrix metabolismus   MeSH
• lidé MeSH
• mechanický stres MeSH
• nádorové buněčné linie MeSH
• oligopeptidy chemie   MeSH
• protoonkogenní proteiny c-yes metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

According to previous studies, integrins play an important role in the mechanotransduction. The aim of this study was to examine the role of integrin subunits and its down-stream signaling molecules in the cyclic hydrodynamic pressure-induced proliferation of human bladder smooth muscle cells (HBSMCs) cultured in scaffolds. The HBSMCs cultured in scaffolds were subjected to four different levels of cyclic hydrodynamic pressure for 24 hours, which were controlled by a BOSE BioDynamic bioreactor. Flow cytometry was used to examine cell cycle distribution. Real-time RT-PCR and western blotting were used to examine the expression levels of integrin subunits and their downstream signaling molecules. Integrin alpha5 siRNA was applied to validate the role of integrin alpha5 in cell proliferation. Here, we showed that cyclic hydrodynamic pressure promoted proliferation of HBSMCs. The cyclic hydrodynamic pressure also increased expression of integrin alpha5 and phosphorylation of FAK, the key mediator of integrin alpha5 signaling, but not that of integrin alpha1, alpha3, alpha4, alphav, beta1 and beta3. Moreover, inhibition of integrin alpha5 decreased the level of p-FAK and abolished proliferation of HBSMCs stimulated by cyclic hydrodynamic pressure. Taken together, we demonstrate for the ?rst time that the integrin alpha5-FAK signaling pathway controls the proliferation of HBSMCs in response to cyclic hydrodynamic pressure.

• MeSH
• buněčný převod mechanických signálů fyziologie   MeSH
• fokální adhezní kinasa 1 biosyntéza   MeSH
• hydrodynamika * MeSH
• integrin alfa5 biosyntéza   MeSH
• kultivované buňky MeSH
• lidé MeSH
• močový měchýř cytologie   metabolismus   MeSH
• myocyty hladké svaloviny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Physicochemical interactions between the cell and its environment are crucial for morphogenesis, tissue homeostasis, remodeling and pathogenesis. Cells form specialized structures like focal adhesions and podosomes that are responsible for bi-directional information exchange between the cell and its surroundings. Besides their role in the transmission of regulatory signals, these structures are also involved in mechanosensing and mechanotransduction. In the past few years, many research groups have been trying to elucidate the mechanisms and consequences of the mechanosensitivity of cells. In this review we discuss the role of the integrin pathway in cellular mechanosensing, focusing on primary mechanosensors, molecules that respond to mechanical stress by changing their conformation. We propose mechanisms by which p130Cas is involved in this process, and emphasize the importance of mechanosensing in cell physiology and the development of diseases.

• MeSH
• buněčné výběžky metabolismus   MeSH
• buněčný převod mechanických signálů fyziologie   MeSH
• fokální adheze metabolismus   MeSH
• integriny metabolismus   MeSH
• lidé MeSH
• mechanický stres MeSH
• mikrofilamenta metabolismus   MeSH
• substrátový protein asociovaný s Crk metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.

• MeSH
• buněčný převod mechanických signálů fyziologie   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• neurogeneze fyziologie   MeSH
• neurony cytologie   MeSH
• neuroplasticita fyziologie   MeSH
• počítačové zpracování obrazu metody   MeSH
• proteiny nervové tkáně metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can be mechanically determined and affect the AS of mRNAs involved in mechanotransduction and cardiovascular diseases, including Hippo pathway effector Yes-associated protein 1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by affecting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNA homeostatic mechanoregulation in pathological conditions.

• MeSH
• buněčný převod mechanických signálů MeSH
• extracelulární matrix metabolismus   MeSH
• heterogenní jaderné ribonukleoproteiny skupiny C * metabolismus   MeSH
• kardiomyocyty metabolismus   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• srdeční selhání * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buněčný převod mechanických signálů fyziologie   MeSH
• lidé MeSH
• nervová zakončení fyziologie   MeSH
• nervové receptory fyziologie   MeSH
• nociceptivní bolest patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH