Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Ss, An; Kim, J; Ahn, Kwangmi; Kumar, Sarmishtha; Biswal, Sibani Lisa

doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5063

Cited by 3 publications

(4 citation statements)

References 12 publications

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“…Existing in vitro and ex vivo models of ASM contractile function have been able to demonstrate the importance of the ECM environment and mechanical loads that oppose ASM contraction (1,12,17,32,39), but these approaches have methodological limitations that prevent them from replicating the full gamut of biomechanical changes thought to occur in asthma. Specifically, traditional 2D culture techniques present a nonphysiological mechanical environment, whereas the ability of ex vivo tissue to recapitulate chronic remodeling events is somewhat limited.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been consistently demonstrated in single cells and ex vivo ASM strips that ECM protein composition can modulate ASM proliferation, contractile protein expression, and contractile function (1,17,32). Similarly, collagenase digestion of ex vivo ASM strips (12) and precision-cut lung slices (39) increases apparent ASM contraction by acutely reducing the load that ECM stiffness presents to oppose contraction.…”

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confidence: 99%

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Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle

West

Zaman

Cole

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Airway smooth muscle (ASM) cellular and molecular biology is typically studied with single-cell cultures grown on flat 2D substrates. However, cells in vivo exist as part of complex 3D structures, and it is well established in other cell types that altering substrate geometry exerts potent effects on phenotype and function. These factors may be especially relevant to asthma, a disease characterized by structural remodeling of the airway wall, and highlights a need for more physiologically relevant models of ASM function. We utilized a tissue engineering platform known as microfabricated tissue gauges to develop a 3D culture model of ASM featuring arrays of ϳ0.4 mm long, ϳ350 cell "microtissues" capable of simultaneous contractile force measurement and cell-level microscopy. ASM-only microtissues generated baseline tension, exhibited strong cellular organization, and developed actin stress fibers, but lost structural integrity and dissociated from the cantilevers within 3 days. Addition of 3T3-fibroblasts dramatically improved survival times without affecting tension development or morphology. ASM-3T3 microtissues contracted similarly to ex vivo ASM, exhibiting reproducible responses to a range of contractile and relaxant agents. Compared with 2D cultures, microtissues demonstrated identical responses to acetylcholine and KCl, but not histamine, forskolin, or cytochalasin D, suggesting that contractility is regulated by substrate geometry. Microtissues represent a novel model for studying ASM, incorporating a physiological 3D structure, realistic mechanical environment, coculture of multiple cells types, and comparable contractile properties to existing models. This new model allows for rapid screening of biochemical and mechanical factors to provide insight into ASM dysfunction in asthma. 3D culture; tissue engineering; asthma; airway smooth muscle; airway wall remodeling ASTHMA IS AN OBSTRUCTIVE AIRWAY disease characterized by increased airway resistance and hyperresponsiveness (AHR) to certain environmental stimuli. The primary cause of AHR is not clear but ultimately it is airway smooth muscle (ASM) contraction that is responsible for airway narrowing. Alterations in sensitivity, force generation, or shortening velocity of ASM in response to contractile agonists may be possible disease mechanisms. It is now also well established that asthma is characterized by airway wall remodeling, which includes thickening of the airway wall and increased ASM mass (52), altered extracellular matrix (ECM) composition (4, 19), infiltration of inflammatory cells (9), and epithelial dysfunction (33). Since airway wall remodeling may precede clinical symptoms (7), it is possible that a putative defect in ASM contractile function arises as a result of the remodeling process. Structural changes in the airway wall may manifest as altered mechanical loads that alter how ASM force development translates into airway narrowing. Such changes could also modulate ASM contractile phenotype through ECM signaling and mechanotransduction, b...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle

West

Zaman

Cole

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…38 Numerous reports exist in the literature underlining the effects of substrate stiffness on cellular behavior and ultimately on successful tissue engineering. 29,39,40 Modular systems were previously shown to provide a platform for the generation of biomaterials with tailored mechanical and biological properties according to applications. 3 Here, we show a simple way to achieve biocompatible cross-linked, modular biomaterials based on elastin, hyaluronan, and silk.…”

Section: Discussionmentioning

confidence: 99%

Modular Elastic Patches: Mechanical and Biological Effects

et al. 2010

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A modular approach to engineering crosslinked elastic biomaterials is presented for fine tuning of material mechanical and biological properties. The three components, soluble elastin, hyaluronic acid and silk fibroin, contribute with different features to the overall properties of the final material system. The elastic biomaterial is chemically crosslinked via interaction between primary amine groups naturally present on the two proteins, silk and elastin, or chemically introduced on hyaluronan and N-succinimide functionalities of the crosslinker. The materials obtained by crosslinking the three components in different ratios have Young's moduli ranging from ~700 kPa to 100 kPa, strain to failure between ~ 65-15 % and ultimate tensile strengths of ~ 50 to 20 kPa. The biological effects and enzymatic degradation rates of the different composites are also different based on material composition. These findings further underline the strength of modular, multi-component systems in creating a range of biomaterials, targeted tissue engineering and regenerative medicine applications, with application-tailored mechanical and biological properties.

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“…The dynamic changes in CSMC run through the entire labor process [7], whereby soft cervical extracellular matrix may lead to decreased CSMC contractile tone and cervical length (supplementary figure). Moreover, the predisposition to sphincter laxity contributes to PTB [8]. Endocrine abnormalities, immune-mediated inflammatory reactions, abnormal gap junction of cervical myocytes, and changes in calcium channels caused by various factors may also induce cervical maturation [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Metabonomics profile analysis in inflammation-induced preterm birth and the potential role of metabolites in regulating premature cervical ripening

Yan

et al. 2022

Reprod Biol Endocrinol

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Background Preterm birth (PTB) is the primary cause of infant morbidity and mortality. Moreover, previous studies have established that PTB is related to premature cervical ripening. However, the underlying mechanism remains to be elucidated. This study sought to identify differentially expressed metabolites and investigate their potential biological functions in PTB. Methods Pregnant C57BL/6 J mice were treated with either LPS or normal saline and cervical alterations before labor were detected by staining. Metabolic profiles in the plasma of PTB and control mice were examined through non-targeted metabonomics analyses, quantitative polymerase chain reaction and immunofluorescence staining were performed on human cervical smooth cells. Results The study demonstrated that the mRNA and protein levels of α-SMA, SM-22, and calponin in cervical smooth muscle cells of PTB mice were lower while OR was higher at both mRNA and protein levels compared to the CTL group. A total of 181 differentially expressed metabolites were analyzed, among them, 96 were upregulated, while 85 were downregulated in the PTB group. Differentially expressed metabolites may play a role in STAT3, RhoA, mTOR, TGF-β, and NK-κB signaling pathways. Furthermore, when treated with taurine, the levels of α-SMA and SM-22 in human cervical smooth muscle cells were elevated, whereas that of connexin-43 was decreased. Conclusion Our study highlighted the changes of metabolites in the peripheral blood changed prior to PTB and revealed that these differentially expressed metabolites might participate in the development of premature cervical ripening. Taurine was identified as an important metabolite may modulate human cervical smooth muscle cells. Our study provided new insights into the mechanism underlying premature cervical ripening in PTB.

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Cell Stiffness, Contractile Stress and the Role of the Extracellular Matrix.

Cited by 3 publications

References 12 publications

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle

Modular Elastic Patches: Mechanical and Biological Effects

Metabonomics profile analysis in inflammation-induced preterm birth and the potential role of metabolites in regulating premature cervical ripening

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