Connective tissue morphogenesis by fibroblast traction

We review the dynamic patterns of cell behaviours in the marginal zone of amphibians with a focus on how the progressive nature and the geometry of these behaviours drive blastopore closure. Mediolateral cell intercalation behaviour and epithelial-mesenchymal transition are used in different combinations in several species of amphibian to generate a conserved pattern of circumblastoporal hoop stresses. Although these cell behaviours are quite different and involve different germ layers and tissue organization, they are expressed in similar patterns. They are expressed progressively along presumptive lateral-medial and anterior-posterior axes of the body plan in highly ordered geometries of functional significance in the context of the biomechanics of blastopore closure, thereby accounting for the production of similar patterns of circumblastoporal forces. It is not the nature of the cell behaviour alone, but the context, the biomechanical connectivity and spatial and temporal pattern of its expression that determine specificity of morphogenic output during gastrulation and blastopore closure. Understanding the patterning of these dynamic features of cell behaviour is important and will require analysis of signalling at much greater spatial and temporal resolution than that has been typical in the analysis of patterning tissue differentiation.

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“…(b) Adapted from Elsdale & Wasoff (1976) and (c) adapted from Stopak & Harris (1982). Shook et al 2002Shook et al , 2004.…”

Section: Epithelial-mesenchymal Transition In the Imz Generates Convementioning

confidence: 99%

Dynamic determinations: patterning the cell behaviours that close the amphibian blastopore

Keller

Shook

2008

Phil. Trans. R. Soc. B

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“…In marked contrast, cells in anchored matrices become bipolar and orient along lines of tension (Stopak and Harris, 1982;Bellows et al, 1982). Cells develop prominent stress fibers and fibronexus junctions and resemble myofibroblasts (Farsi and Aubin, 1984;Mochitate et al, 1991;Tomasek et al, 1992).…”

Section: Collagen Matrix Contraction and The Cell Phenotypementioning

confidence: 99%

Fibroblasts, myofibroblasts, and wound contraction

Grinnell

1994

The Journal of Cell Biology

1,035

752

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“…Centimeter scale encapsulations of cells in ECM analogues are widely used as model systems for many morphogenetic processes (8)(9)(10)(11). However, although such systems can recapitulate many developmental processes, the cellular forces within these encapsulations are typically inferred only indirectly by measuring the volumetric contraction of free-floating constructs, or from the population average of constructs pulling against rigid strain gauges (12, 13).…”

mentioning

confidence: 99%

Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues

Legant

Pathak

Yang

et al. 2009

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

380

442

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Physical forces generated by cells drive morphologic changes during development and can feedback to regulate cellular phenotypes. Because these phenomena typically occur within a 3-dimensional (3D) matrix in vivo, we used microelectromechanical systems (MEMS) technology to generate arrays of microtissues consisting of cells encapsulated within 3D micropatterned matrices. Microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process. By concurrently measuring forces and observing matrix remodeling at cellular length scales, we report an initial correlation and later decoupling between cellular contractile forces and changes in tissue morphology. Independently varying the mechanical stiffness of the cantilevers and collagen matrix revealed that cellular forces increased with boundary or matrix rigidity whereas levels of cytoskeletal and extracellular matrix (ECM) proteins correlated with levels of mechanical stress. By mapping these relationships between cellular and matrix mechanics, cellular forces, and protein expression onto a bio-chemo-mechanical model of microtissue contractility, we demonstrate how intratissue gradients of mechanical stress can emerge from collective cellular contractility and finally, how such gradients can be used to engineer protein composition and organization within a 3D tissue. Together, these findings highlight a complex and dynamic relationship between cellular forces, ECM remodeling, and cellular phenotype and describe a system to study and apply this relationship within engineered 3D microtissues.biomechanics ͉ cell mechanics ͉ collagen ͉ morphogenesis ͉ PDMS

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Connective tissue morphogenesis by fibroblast traction

Cited by 562 publications

References 21 publications

Dynamic determinations: patterning the cell behaviours that close the amphibian blastopore

Dynamic determinations: patterning the cell behaviours that close the amphibian blastopore

Fibroblasts, myofibroblasts, and wound contraction

Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues

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