Directed Movement of Vascular Smooth Muscle Cells on Gradient-Compliant Hydrogels

Wong, Joyce Y.; Velasco, A Marco; Rajagopalan, Padmavathy; Pham, Quynh P.

doi:10.1021/la026403p

Cited by 425 publications

(422 citation statements)

References 25 publications

(43 reference statements)

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“…Fibroblasts on elastic substrates orient in the direction of tensile strain (6) and locomote in favor of regions of larger rigidity or tensile strain (7). The same response has been reported for vascular smooth muscle cells on rigidity gradients (8). Similar observations have been reported numerous times also for tissue cells in hydrogels.…”

supporting

confidence: 77%

Cell organization in soft media due to active mechanosensing

Bischofs

Schwarz

2003

Proc. Natl. Acad. Sci. U.S.A.

291

263

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Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain; they orient parallel and normal to free and clamped surfaces, respectively; and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover, our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are up-regulated by large effective stiffness in the environment because, in this way, build-up of force is more efficient.T he mechanical activity of adherent cells usually is attributed to their physiological function. For example, fibroblasts are believed to maintain the structural integrity of connective tissue and to participate in wound healing by actively pulling on their environment. During recent years, it has become clear that there is another important role for mechanical activity of adherent cells: by pulling on their environment, cells can actively sense its mechanical properties and react to it in a specific way (1-3). Harris et al. (4) observed surprisingly large tension fields for fibroblasts on elastic substrates, which induce mechanical activity of other cells, even when located at considerable distance. When plated on elastic substrates of increased rigidity, many cell types show increased spreading and better developed stress fibers and focal adhesions (5). Fibroblasts on elastic substrates orient in the direction of tensile strain (6) and locomote in favor of regions of larger rigidity or tensile strain (7). The same response has been reported for vascular smooth muscle cells on rigidity gradients (8). Similar observations have been reported numerous times also for tissue cells in hydrogels. For fibroblasts in collagen gels, Bell et al. (9) not only found that traction considerably contracts the gel, but also reported orientational effects: cells align along the direction of pull between fixed points and parallel to free surfaces. When a collagen gel is stretched uniaxially, cells orient in the direction of principal strain (10). Moreover, cells align in a nose-to-tail configuration, thus forming strings running in parallel to the direction of external strain. If a collagen gel is cut perpendicular to the direction of tensile strain and if cells are present in sufficient numbers, they round up and reorient parallel to the free surface introduced (11).The response of adherent animal cells to mechanical input ...

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supporting

confidence: 77%

Cell organization in soft media due to active mechanosensing

Bischofs

Schwarz

2003

Proc. Natl. Acad. Sci. U.S.A.

291

263

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“…Cell migration is also tightly regulated by cell adhesion, cell-generated contractility and cell haptotaxis to maximize their ligand binding and even duro-taxis towards a stiffer matrix to increase cell tension (Sheetz, Felsenfeld, & Galbraith, 1998;Wong, Velasco, Rajagopalan, & Pham, 2003). This suggests that elevated matrix deposition and tension likely couple with degradation to modulate tumor invasion and metastasis.…”

Section: Associated Pathologiesmentioning

confidence: 99%

Mammary epithelial cell: Influence of extracellular matrix composition and organization during development and tumorigenesis

Kass

Erler

Dembo

et al. 2007

The International Journal of Biochemistry & Cell Biology

275

220

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Stromal-epithelial interactions regulate mammary gland development and are critical for the maintenance of tissue homeostasis. The extracellular matrix, which is a proteinaceous component of the stroma, regulates mammary epithelial growth, survival, migration and differentiation through a repertoire of transmembrane receptors, of which integrins are the best characterized. Integrins modulate cell fate by reciprocally transducing biochemical and biophysical cues between the cell and the extracellular matrix, facilitating processes such as embryonic branching morphogenesis and lactation in the mammary gland. During breast development and cancer progression, the extracellular matrix is dynamically altered such that its composition, turnover, processing and orientation change dramatically. These modifications influence mammary epithelial cell shape, and modulate growth factor and hormonal responses to regulate processes including branching morphogenesis and alveolar differentiation. Malignant transformation of the breast is also associated with significant matrix remodeling and a progressive stiffening of the stroma that can enhance mammary epithelial cell growth, perturb breast tissue organization, and promote cell invasion and survival. In this review, we discuss the role of stromal-epithelial interactions in normal and malignant mammary epithelial cell behavior. We specifically focus on how dynamic modulation of the biochemical and biophysical properties of the extracellular matrix elicit a dialogue with the mammary epithelium through transmembrane integrin receptors to influence tissue morphogenesis, homeostasis and malignant transformation. Keywords NIH Public AccessAuthor Manuscript Int J Biochem Cell Biol. Author manuscript; available in PMC 2009 March 19. Published in final edited form as:Int J Biochem Cell Biol. 2007 ; 39(11): 1987-1994. doi:10.1016/j.biocel.2007.025. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptCell facts• Stromal-epithelial interactions regulate mammary epithelial cell growth and differentiation during embryonic and postnatal development.• The spatial organization and composition of the extracellular matrix influence mammary epithelial cell behavior.• Alterations in extracellular matrix receptor expression can enable malignant transformation of the mammary epithelial cells.• Differences in the biophysical properties of the extracellular matrix due to an increase in deposit and/or cross-linking can induce the malignant transformation of mammary epithelial cells.

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“…While it is clear that the transport of oosperm involves smooth muscle contraction [1,2], the detailed mechanism still remains elusive [1][2][3][4][5][6][7], due in part to the complexity of cellsubstrate interactions via receptor-ligand binding as well as various physical forces inside and outside of the cytoskeleton [8][9][10][11][12]. Cells are known to respond to mechanical forces exerted through surrounding fluid, adhering beads or substrates [9,[12][13][14], and they could detach, slip or roll on a substrate in response to these forces [15][16][17][18][19][20][21][22]. For example, cells on a cyclically stretched substrate tend to reorient themselves away from the stretching direction [23][24][25][26][27], and cells migrate along a substrate with rigidity gradient (durotaxis) [18].…”

Section: Introductionmentioning

confidence: 99%