Traction microscopy with integrated microfluidics: responses of the multi-cellular island to gradients of HGF

Jang, Hwanseok; Kim, Jong‐Seong; Shin, Jennifer Hyunjong; Fredberg, Jeffrey J.; Park, Chan Young; Park, Yongdoo

doi:10.1039/c9lc00173e

Cited by 14 publications

(8 citation statements)

References 67 publications

(71 reference statements)

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“…Since observation of the dynamics of these cell clusters is limited using conventional biological methods, biophysical methods, such as TFM, have allowed the mechanisms of collective cell behavior to be studied and more clearly understood [ 33 ]. In this study, in order to quantify the dynamics of the movement and physical force of collective cells under a fluid flow environment, a traction force-measurable microfluidic chip was developed by improving upon the system developed in our previous study [ 28 ]. The microchannel in the inlet and outlet was designed in the shape of a tree branch such that a constant flow rate was evenly distributed over the cell islands arranged in the channel.…”

Section: Discussionmentioning

confidence: 99%

“…Phase contrast cell and fluorescent bead images obtained by time-lapse microscopy were computed to quantify cellular motility and force using the customized MATLAB code used in previous studies [ 27 , 28 ]. Briefly, at each time point, the cell image and its next cell image or bead image and the reference bead image were calculated using a particle image velocimetry (PIV) algorithm based on cross-correlation (calculation of correlation between serial cell images).…”

Section: Methodsmentioning

confidence: 99%

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Study on the Expansion Dynamics of MDCK Epithelium by Interstitial Flow Using a Traction Force-Measurable Microfluidic Chip

2021

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The movement of collective cells is affected through changes in physical interactions of cells in response to external mechanical stimuli, including fluid flow. Most tissues are affected by fluid flow at the interstitial level, but few studies have investigated the physical effects in collective cells affected by a low flow rate. In this study, collective cell migration of Madin–Darby canine kidney (MDCK) epithelial cells was investigated under static or interstitial flow (0, 0.1, and 1 μL/min) using a traction microfluidic device. The optimization of calculation of cellular traction forces was first achieved by changing interrogation window size from the fluorescent bead images. Migration analysis of cell collectives patterned with a 700 μm circular shape reveals that cells under the slow flow (0.1 and 1 μL/min) showed the inhibitory migration by decreasing cell island size and cellular speed compared to that of static condition. Analysis of cellular forces shows that level of traction forces was lower in the slow flow condition (~20 Pa) compared to that of static condition (~50 Pa). Interestingly, the standard deviation of traction force of cells was dramatically decreased as the flow rate increased from 0 to 1 μL/min, which indicates that flow affects the distribution of cellular traction forces among cell collectives. Cellular tension was increased by 50% in the cells under the fluid flow rate of 1 μL/min. Treatment of calcium blocker increased the migratory speed of cells under the flow condition, whereas there is little change of cellular forces. In conclusion, it has been shown that the interstitial flow inhibited the collective movement of epithelial cells by decreasing and re-distributing cellular forces. These findings provide insights into the study of the effect of interstitial flow on cellular behavior, such as development, regeneration, and morphogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Study on the Expansion Dynamics of MDCK Epithelium by Interstitial Flow Using a Traction Force-Measurable Microfluidic Chip

2021

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“…The acquired bright-field cell images were numerically transformed and quantitatively analyzed using custom codes written in MATLAB (MathWorks Inc., Portola Valley, CA, USA). The codes used in this study to extract cell displacements and velocities are based on the particle image velocimetry (PIV) code used in the previous study [ 24 , 25 ]. The consecutive cell island images of 1216 × 1216 pixels (1070 × 1070 μm) taken at 10 min intervals were cross-correlated using unit pixel subset windows (interrogation windows, IWs) of 64 × 64 pixels at a spacing of 16 pixels (14 μm).…”

Section: Methodsmentioning

confidence: 99%

“…Especially, the free edge migration model using a micro-sized stencil is a simple and ideal tool to investigate the collective cell migration [ 23 , 24 ]. Analysis of cellular kinematics and force distribution based on patterning technology showed that cell-cell junction such as cadherin and redistribution of vinculin is important to control the collective cell migration [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

et al. 2021

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Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial–mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

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“…Regardless, these methodologies, broadly referred to as traction force microscopy (TFM), continue to yield insightful biological trends linking cell‐generated forces to biological phenomena (Figure 2). [ 141,156–158 ]…”

Section: Measuring Cell and Tissue Mechanical Properties For Mechanotmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Traction microscopy with integrated microfluidics: responses of the multi-cellular island to gradients of HGF

Abstract: Microfluidic system integrated with cell collectives and traction microscopy demonstrates that collective cell migration plays a central role in development, regeneration, and metastasis.

Cited by 14 publications

References 67 publications

Study on the Expansion Dynamics of MDCK Epithelium by Interstitial Flow Using a Traction Force-Measurable Microfluidic Chip

Study on the Expansion Dynamics of MDCK Epithelium by Interstitial Flow Using a Traction Force-Measurable Microfluidic Chip

Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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