Local force and geometry sensing regulate cell functions

Vogel, Viola; Sheetz, Michael P.

doi:10.1038/nrm1890

Cited by 2,090 publications

(1,697 citation statements)

References 159 publications

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“…(Baneyx et al 2002;Mao and Schwarzbauer 2005;Abu-Lail et al 2006) This elasticity appears to come from unfolding domains of fibronectin and shifting to extended molecular conformations. (Baneyx et al 2002;Abu-Lail et al 2006;Vogel and Sheetz 2006) As discussed later, mechanical stretching of TM cells and their ECMs triggers homeostatic responses that reduce the outflow resistance. These fibronectin fibrils, which would have a number of cellular integrin attachments for each fibril, would provide an ideal sensing structure to communicate IOP-induced mechanical stretch to TM cells.…”

Section: Fibronectin and Vitronectinmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear.The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region.The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.

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Section: Fibronectin and Vitronectinmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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“…The relationship of cell adhesion and motility to the substrate stiffness has become the focus of major studies in recent years (Bershadsky et al, 2006;Geiger and Bershadsky, 2001;Georges and Janmey, 2005;Rehfeldt et al, 2007;Vogel and Sheetz, 2006). It has been found that force sensing and substrate stiffness define the formation and turnover of the adhesions to the extracellular matrix and determine the speed of migration, as well as cell shape and ability to differentiate (Engler et al, 2006).…”

Section: Extracellular Matrix and Force Sensing: Paving The Pathways mentioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

117

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Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni-and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra-and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.

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“…In addition to soluble biochemical cues such as growth factors and cytokines, cells are also known to sense and respond to physical factors, including the mechanical properties of their environment (as reviewed in Discher et al, 2005;Ingber, 2006;Vogel and Sheetz, 2006) and the local topography of their substrates (Dalby et al, 2004;Dalby et al, 2005). Differences in substrate rigidity (Engler et al, 2006;Galbraith et al, 2002;Giannone and Sheetz, 2006;Kostic and Sheetz, 2006;Yeung et al, 2005) as well as micro-and nanoscale features (Dalby et al, 2005) have been correlated with profound effects on cell adhesion, morphology, proliferation, and gene regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Yet, the underlying molecular mechanisms by which physical factors, including force and the mechanical properties of matrices, are converted into biochemical signals that ultimately regulate protein expression are only beginning to be explored (Kostic and Sheetz, 2006). One focus is to identify proteins whose structure/function relationship can be altered by mechanical forces, causing for example the opening of ion channels, a change in the spatial presentation of binding sites, or the exposure of otherwise cryptic binding sites (for reviews see Bustamante et al, 2004;Kung, 2005;Vogel, 2006;Vogel and Sheetz, 2006;Arcangeli and Becchetti, 2006).…”

Section: Introductionmentioning

confidence: 99%

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

et al. 2008

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In response to growing needs for quantitative biochemical and cellular assays that address whether the extracellular matrix (ECM) acts as a mechanochemical signal converter to co-regulate cellular mechanotransduction processes, a new assay is presented where plasma fibronectin fibers are manually deposited onto elastic sheets, while force-induced changes in protein conformation are monitored by fluorescence resonance energy transfer (FRET). Fully relaxed assay fibers can be stretched at least 5-6 fold, which involves Fn domain unfolding, before the fibers break. In native fibroblast ECM, this full range of stretch-regulated conformations coexists in every field of view confirming that the assay fibers are physiologically relevant model systems. Since alterations of protein function will directly correlate with their extension in response to force, the FRET vs. strain curves presented herein enable the mapping of fibronectin strain distributions in 2D and 3D cell cultures with high spatial resolution. Finally, cryptic sites for fibronectin's N-terminal 70-kD fragment were found to be exposed at relatively low strain, demonstrating the assay's potential to analyze stretch-regulated protein-rotein interactions.

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Local force and geometry sensing regulate cell functions

Cited by 2,090 publications

References 159 publications

Extracellular matrix in the trabecular meshwork

Extracellular matrix in the trabecular meshwork

Cell biology of embryonic migration

Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage

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