Cell Structure Controls Endothelial Cell Migration under Fluid Shear Stress

Lin, Xiefan; Helmke, Brian P.

doi:10.1007/s12195-009-0060-z

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…In both the fibroblastic cultures and chondrocytic chondrocyte cultures, TGF-β1 seemed to induce a further wound enlargement. This may indicate that TGF-β1 may play a part in inducing a stress response in chondrocytic cells similar to that described by Lin and Helmke (2009) and a production of nitric oxide, consequently induction in cell death [13] as described by Im and Shin (2002). This may play a part in the down regulation of chondrocyte mitogenesis.…”

Section: Wound Repairmentioning

confidence: 66%

Effect of Transforming Growth Factor-β1 in Biological Regulation of Primary Chondrocyte

Khaghani

Denyer²,

Youseffi³

2012

AJBE

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The effect of transforming growth factors-β (TGF-βs) in the regulation and control of cell growth is widely studied, but the capability of these cytokines to regulate chondrocyte cell functions such as migration, cell death, proliferation, differentiation and wound repair is not clearly understood. In this work the effect of TGF-β1 on the biological regulation of chondrocyte was evaluated using a model wound closure assay. The experiments were carried out on primary chondrocyte cells with fibroblast like and chondrocytic phenotypes. The cells were isolated from knee articular cartilage of five day old Sprague-Dawley neonate rats and seeded at low density to obtain a fibroblast like morphology. Chondrocytes with chondrocytic phenotype were derived by seeding at high density.The results revealed that TGF-β1 slowed down proliferation and migration of cells into a model wound. It was also found that cell attachment, as determined by the detachment time during trypsinization, was greater for cells with a fibroblast like morphology when compared with cells exhibiting chondrocytic morphology. Treatment with TGF-β1 was found to increase the detachment times of fibroblast like chondrocytes, indicating that TGF-β1enhanced cell attachment of this cell type, whilst treatment with TGF-β1 decreased detachment time for the chondrocytic type chondrocyte cells indicating that TGF-β1 decreased cell attachment in these cells.

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Section: Wound Repairmentioning

confidence: 66%

Effect of Transforming Growth Factor-β1 in Biological Regulation of Primary Chondrocyte

Khaghani

Denyer²,

Youseffi³

2012

AJBE

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“…Lin and Helmke demonstrated that migration direction is a function of geometry and confluency and that nonconfluent endothelial cells undergo triphasic mechanotaxis, as opposed to endothelial cells in a confluent monolayer, which migrate downstream immediately upon application of shear flow (46). In addition to forces on the cell being pressure dominated rather than shear dominated for cells in 3D, recent work has demonstrated that migration in 3D is much different from 2D migration, and Fraley et al have demonstrated that migration in 3D is predominantly governed by pseudopod activity and matrix deformation (20).…”

Section: Discussionmentioning

confidence: 99%

Interstitial flow influences direction of tumor cell migration through competing mechanisms

Polacheck¹,

Charest

Kamm

2011

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

433

434

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Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526-538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease. mechanobiology | computational model | signaling | cell mechanics T issues are composed of cells residing in an extracellular matrix (ECM) containing interstitial fluid that transports nutrients and signaling molecules (1, 2). Osmotic and hydrostatic pressure gradients across tissues resulting from physiologic processes such as drainage toward lymphatics, inflammation, locally elevated pressures due to tumor growth or leaky microvessels, and muscle contraction each drive fluid flow through the ECM (2, 3). This fluid flow is termed interstitial flow and has long been recognized to be instrumental in tissue transport and physiology (1, 4, 5). Chary and Jain used fluorescence recovery after photobleaching to directly observe fluid flow in the tissue interstitium and determined typical flow velocities to be on the order of 0.1-2.0 μm/s, and more recent studies have demonstrated that flow can reach velocities as high as 4.0 μm/s (6, 7).Interstitial flow is particularly important in driving transport in the vicinity of tumors, as neoplastic tissue is often characterized by localized increases in interstitial pressure, leading to high interstitial pressure gradients at the tumor margin (8). Interstitial flow has hence emerged as a possible stimulus for guiding tumor cell migration in the formation of metastases (9-12).Shields et al. observed increase...

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“…For instance, by culturing ECs on micropatterned extracellular matrix, Lin et al demonstrated that ECs with different morphologies respond to shear stress differently. 23,24 In particular, they observed that when shear stress was applied to ECs with polygonal shapes, the cells first migrated upstream. However, over time, the ECs switched their direction of migration to downstream.…”

Section: Vasculaturementioning

confidence: 99%

Microfluidic platforms for mechanobiology

et al. 2013

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Mechanotransduction has been a topic of considerable interest since early studies demonstrated a link between mechanical force and biological response. Until recently, studies of fundamental phenomena were based either on in vivo experiments with limited control or direct access, or on large-scale in vitro studies lacking many of the potentially important physiological factors. With the advent of microfluidics, many of the previous limitations of in vitro testing were eliminated or reduced through greater control or combined functionalities. At the same time, imaging capabilities were tremendously enhanced. In this review, we discuss how microfluidics has transformed the study of mechanotransduction. This is done in the context of the various cell types that exhibit force-induced responses and the new biological insights that have been elucidated. We also discuss new microfluidic studies that could produce even more realistic models of in vivo conditions by combining multiple stimuli or creating a more realistic microenvironment.

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Cell Structure Controls Endothelial Cell Migration under Fluid Shear Stress

Cited by 9 publications

References 33 publications

Effect of Transforming Growth Factor-β1 in Biological Regulation of Primary Chondrocyte

Effect of Transforming Growth Factor-β1 in Biological Regulation of Primary Chondrocyte

Interstitial flow influences direction of tumor cell migration through competing mechanisms

Microfluidic platforms for mechanobiology

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