Thickness sensing of hMSCs on collagen gel directs stem cell fate

Leong, Wen Shing; Tay, Chor Yong; Yu, Haiyue; Li, Ang; Wu, Shucheng; Duong-Hong, Duc; Lim, Chwee Teck; Tan, Lay Poh

doi:10.1016/j.bbrc.2010.09.052

Cited by 75 publications

(71 citation statements)

References 31 publications

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“…We cultured cells on the surface of attached (glass-supported) or floating collagen gels to assess mechanosensation in the presence or absence of a rigid foundation. Cells were well spread on attached collagen matrices (collagen concentrations of 1 mg ml 21 or 3 mg ml 21 ; figure 7a,b), consistent with previous data [34,35]. By contrast, cells were less spread and exhibited sparse (n , 4), thin and relatively short cell extensions when cultured on floating gels ( figure 7c,d).…”

Section: Cell Mechanosensationsupporting

confidence: 89%

“…In this report, we used relatively wide, thin floating collagen matrices supported at their edges by nylon grids to study cell -matrix interactions unencumbered by external environmental factors such as the presence of lateral and underlying physical boundaries [20,34]. This model enables comparisons with cells on thin collagen matrices supported by an underlying rigid foundation without changing the thickness of the collagen.…”

Section: Discussionmentioning

confidence: 99%

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Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

Mohammadi

Arora

Simmons

et al. 2015

J. R. Soc. Interface.

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The mechanical properties of extracellular matrix proteins strongly influence cell-induced tension in the matrix, which in turn influences cell function. Despite progress on the impact of elastic behaviour of matrix proteins on cell-matrix interactions, little is known about the influence of inelastic behaviour, especially at the large and slow deformations that characterize cell-induced matrix remodelling. We found that collagen matrices exhibit deformation rate-dependent behaviour, which leads to a transition from pronounced elastic behaviour at fast deformations to substantially inelastic behaviour at slow deformations (1 mm min 21, similar to cell-mediated deformation). With slow deformations, the inelastic behaviour of floating gels was sensitive to collagen concentration, whereas attached gels exhibited similar inelastic behaviour independent of collagen concentration. The presence of an underlying rigid support had a similar effect on cell-matrix interactions: cell-induced deformation and remodelling were similar on 1 or 3 mg ml 21 attached collagen gels while deformations were two-to fourfold smaller in floating gels of high compared with low collagen concentration. In cross-linked collagen matrices, which did not exhibit inelastic behaviour, cells did not respond to the presence of the underlying rigid foundation. These data indicate that at the slow rates of collagen compaction generated by fibroblasts, the inelastic responses of collagen gels, which are influenced by collagen concentration and the presence of an underlying rigid foundation, are important determinants of cell-matrix interactions and mechanosensation.

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Section: Cell Mechanosensationsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

Mohammadi

Arora

Simmons

et al. 2015

J. R. Soc. Interface.

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“…There is currently little understanding of how such changes affect epithelial cells. However, phenotypic changes have been demonstrated in other types of cells that were dependent upon the stiffness of the substrate upon which the cells were grown (13,22,134, 151, 153, 242). Furthermore, epithelial mesenchymal transition, in which epithelial cells differentiate into fibroblasts or myofibroblasts, has been shown to occur in human idiopathic pulmonary fibrosis (140,141).…”

Section: Epithelial Responses To Mechanical Forces In Vivomentioning

confidence: 99%

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

Waters

Roan

Navajas

2012

Comprehensive Physiology

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Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis.

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“…31 Concurrently, experimental studies suggest that cells can sense rigid interfaces upwards of 500 lm away. 30,31 Thus, we expect that throughout the 300 lm thick collagen layer, the cells are able to sense and respond to the microfiber layer. Finally, while the incorporation of a sparse fiber layer within collagen gels modulated expression of Scx and a-SMA, the addition of biological cues (e.g., growth factors, morphogens) could facilitate a more complete MSC differentiation into the ligament fibroblast phenotype.…”

Section: Discussionmentioning

confidence: 98%

Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells

Thayer

Verbridge

Dahlgren

et al. 2016

J. Biomed. Mater. Res.

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Electrospun microfibers are attractive for the engineering of oriented tissues because they present instructive topographic and mechanical cues to cells. However, high-density microfiber networks are too cell-impermeable for most tissue applications. Alternatively, the distribution of sparse microfibers within a three-dimensional hydrogel could present instructive cues to guide cell organization while not inhibiting cell behavior. In this study, thin (∼5 fibers thick) layers of aligned microfibers (0.7 μm) were embedded within collagen hydrogels containing mesenchymal stem cells (MSCs), cultured for up to 14 days, and assayed for expression of ligament markers and imaged for cell organization. These microfibers were generated through the electrospinning of polycaprolactone (PCL), poly(ester-urethane) (PEUR), or a 75/25 PEUR/PCL blend to produce microfiber networks with elastic moduli of 31, 15, and 5.6 MPa, respectively. MSCs in composites containing 5.6 MPa fibers exhibited increased expression of the ligament marker scleraxis and the contractile phenotype marker α-smooth muscle actin versus the stiffer fiber composites. Additionally, cells within the 5.6 MPa microfiber composites were more oriented compared to cells within the 15 and 31 MPa microfiber composites. Together, these data indicate that the mechanical properties of microfiber/collagen composites can be tuned for the engineering of ligament and other target tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1894-1901, 2016.

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Thickness sensing of hMSCs on collagen gel directs stem cell fate

Cited by 75 publications

References 31 publications

Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells

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