Mechanobiology in the Third Dimension

Pedersen, John A.; Swartz, Melody A.

doi:10.1007/s10439-005-8159-4

Cited by 366 publications

(327 citation statements)

References 210 publications

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“…In a 3D microenvironment, cells need to either degrade the extracellular matrix (ECM) or squeeze through small pores in amoeboid fashion (Wolf and Friedl 2008), and they may experience chemokine gradients differently, since many are matrix-binding (Patel et al 2001). As a result, cells behave very differently in 3D vs. 2D environments (Behnsen et al 2007;Cukierman et al 2001;Griffith and Swartz 2006;Pedersen and Swartz 2005). Thus, to examine cell migration in a physiologically realistic setting, migration assays need to accurately recapitulate the 3D microenvironment.…”

Section: Introductionmentioning

confidence: 99%

An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies

Haessler

Kalinin

Swartz

et al. 2009

Biomed Microdevices

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The current state-of-art in 3D microfluidic chemotaxis device (μFCD) is limited by the inherent coupling of the fluid flow and chemical concentration gradients. Here, we present an agarose-based 3D μFCD that decouples these two important parameters, in that the flow control channels are separated from the cell compartment by an agarose gel wall. This decoupling is enabled by the transport property of the agarose gel, which-in contrast to the conventional microfabrication material such as polydimethylsiloxane (PDMS)-provides an adequate physical barrier for convective fluid flow while at the same time readily allowing protein diffusion. We demonstrate that in this device, a gradient can be pre-established in an agarose layer above the cell compartment (a gradient buffer) before adding the 3D cell-containing matrix, and the dextran (10 kDa) concentration gradients can be re-established within 10 min across the cell-containing matrix and remain stable indefinitely. We successfully quantified the chemotactic response of murine dendritic cells to a gradient of CCL19, an 8.8 kDa lymphoid chemokine, within a type I collagen matrix. This model system is easy to set up, highly reproducible, and will benefit research on 3D chemoinvasion studies, for example with cancer cells or immune cells. Because of its gradient buffering capacity, it is particularly suitable for studying rapidly migrating cells like mature dendritic cells and neutrophils.

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Section: Introductionmentioning

confidence: 99%

An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies

Haessler

Kalinin

Swartz

et al. 2009

Biomed Microdevices

Self Cite

156

164

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“…A theme of importance that has not seen the limelight, mostly due to absence of in vivo studies, is the role of mechanical communication of keratocytes with their extracellular environment in maintaining corneal structural integrity. Cell-ECM interaction is critical for communicating the state of the mechanical environment to the cell as well as in mediating cellular response to a variety of stimuli (Pedersen and Swartz 2005). We discuss the role of keratocyte-integrins and ECM components in the maintenance of the stromal structure in a normal cornea and the restoration of stromal integrity after corneal disease or injury.…”

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confidence: 99%

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Parapuram

Hodge

2014

J. Cell Commun. Signal.

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Several studies have established the role of activated corneal keratocytes in the fibrosis of the cornea. However, the role of keratocytes in maintaining the structural integrity of a normal cornea is less appreciated. We focus on the probable functions of integrins in the eye and of the importance of integrin-mediated keratocyte interactions with stromal matrix in the maintenance of corneal integrity. We point out that further understanding of how keratocytes interact with their matrix could establish a novel direction in preventing corneal pathology including loss of structural integrity as in keratoconus or as in fibrosis of the corneal stroma.Keywords Cornea . Keratocytes . Corneal stroma . Extracellular matrix . Integrins . KeratoconusThe simple cellular organization of the cornea is belied by its fascinating specialization for transparency. The cornea has three main tissue layers, the outer epithelium, the stroma in the middle and the inner endothelial layer. The stromal connective tissue, the layer mainly responsible for the corneal configuration, constituting nearly 80 % of the thickness of the cornea, is extremely resilient, capable of resisting intraocular pressure and protecting the posterior structures of the eye. The stromal tissue consists of lamellae of orthogonally arranged collagen fibrils surrounded by proteoglycans; in between the lamellae of collagen are found the keratocytes. The nearorderly arrangement of collagen lamellae, the narrow diameter of the collagen fibrils, regular interfibrillar space, associated proteoglycans and the expression of crystalline proteins in the keratocytes (Birk 2001;Kao and Liu 2002;Jester et al. 2007; Hassell and Birk 2010) are some of the main factors responsible for corneal transparency. Consequently, the factors affecting corneal transparency such as fibrotic changes due to disease or injury are problems primarily associated with the stroma. Thus it is important to achieve further understanding of the mechanisms by which the stroma acquires and maintains its structural integrity and its transparency.

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“…Since these studies stretched cells growing in a monolayer, the extracellular matrix that surrounds skin cells was not taken into account. This is important as the responses of skin cells in three-dimensional (2014) 66:723-728 725 cultures are different from those of skin cells in monolayer cultures (Pedersen and Swartz 2005).…”

Section: Resultsmentioning

confidence: 99%

Effect of strain on human dermal fibroblasts in a three-dimensional collagen sponge

et al. 2013

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Our aim was to design a simple compression system and investigate the influence of mechanical stress on skin-like structures. Many mechanical compression studies have employed intricate culture systems, so the relationship between extracellular matrix material and the response of skin cells to mechanical stress remains unknown. Our approach uses only glass vials, 6-well plates and standard laboratory equipment. We examined the influence of mechanical stress on human skin fibroblasts embedded within a collagen sponge. The results show that mechanical compression increases MMP-1 and MMP-2 release by the cells into the the cell culture. Our results suggest that pressure on the skin may affect extracellular matrix degradation through some as yet unidentified pathways and that IL-6 mRNA expression may be involved in this effect. Using our approach, the effects of static mechanical stress on protein expression by cells in the culture medium and in sponges can be easily examined, and therefore this system will be useful for further analyses of skin responses to mechanical stress.

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Mechanobiology in the Third Dimension

Cited by 366 publications

References 210 publications

An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies

An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Effect of strain on human dermal fibroblasts in a three-dimensional collagen sponge

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