Cell deformation using microfluidic chip

Deform and change cells shape using microfluidic chip

HeLa cell deformation using microfluidic device

Cells growth, gene expression and differentiation are often related to mechanical environment such as confinement or applied stresses. The use of microfluidic chip enables to control shape and stress of cells even at a single cell level. You will find here a short description of the use of microfluidics for cell shape confinement.

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Which microfluidic method can be used to control cell shape and stress ?

Using microfluidics, researchers can generate large number of cell shape change and mechanical stress: cells can be dynamically squeezed with a controlled pressure, cells can be forced to grow in a channel of a given geometry or cells can be submitted to a controlled shear stress.

There are three main methods to control the mechanical behavior of cell:

The easiest method is to force cell to grow in a microfluidic channel or chamber of a given shape. For example, non adherent cells such as yeast or bacterias can be forced to enter in microchannels using “high” pressure. Adherent cell such as Hela mammalian cancer cell can be settle in a microfluidic room and forced to grow with a given shape.

Which microfluidic method can be used to control cell shape

Photo : C. R. Terenna, T. Makushok, G. Velve-Casquillas, D. Baigl, Y. Chen, M. Bornens et al., Curr. Biol. 18 (2008) 1748.

The second method enables dynamic cell deformation using deformable “PDMS Quake valve”. In this case, cells can be dynamically squeezed in a controlled manner using fine pressure change.

The last common method is to use shear stress generated by microfluidic flow on adherent cell stuck on the substrate. Changing the flow it becomes possible to change the mechanical stress on cells. Using this method cell can be either submitted to laminar or extensional flow [1]

HeLa cell deformation using microfluidic device

Photo : from mael le berre, institute curie : Hela cell sqeezed using a PDMS quake valve.

Which setup and which microfluidic chip to control cell shape and stresses ?

There are several microfluidic devices design enabling cell shape modification. The choice of the design will depend on your particular experiment. You can have a look to the bibliography below or feel free to contact the Elveflow team (below too) to get advices on own to refine or adapt the design of your chip to your application.

To inject non adherent cell like yeast or bacteria in a microfluidic channel you can simply use a manual syringe to push the cell into a channel with a given shape. It’s the cheapest method, but since it is quite hard to control the pressure with your hand, your cells and microfluidic device can sometimes be damaged. (but I had done it with a syringe during several years and most of my cell survives)

In this particular case, you should particularly avoid syringe pumps, since during the injection the cells will cork your microchannel, the fluidic resistance of your device will increase with time which can lead to a pressure increase which could destroy your microfluidic device. The better way is to use a pressure controller (with a pressure range up to 1 or 2 bar) to be sure that you will not damage cells and device, since the pressure of injection will always be the same.

To dynamically squeezed adherent cell using an integrated PDMS quake valve, you will need to use, here too, a pressure controller. In this case the range of pressure you should use will depend of the cell type. You cannot use syringe pump with quake valve since it will lead to an infinite pressure increase leading to device destruction.

To apply flow shear stress on adherent cell on a substrate you can use either syringe pump or pressure controller. Of course in the case you want high responsiveness (below 1 seconds) and very precise flow at low flow rate , as usual, the use of pressure controller will be recommended.

Applications of cell shape change and mechanical stress

Mechanical deformation of cell using microfluidic device have been used in many situation :

It have been used for studies of cytoskeleton behavior [2], reaction¬diffusion mechanisms [3], to mimic mechanically induced behavior of mechanotransduction [4, 5] or cell motility in confined environment [6], mimic tissue organization like the vasculature system [7] and to study the mechanical properties of cancer cells [8].

If the precise geometry of the cell is not of concern, cells can be macroscopically subjected to stress. Stress can be compressive, as an exemple, to study bone cell responses to mechanical stresses [9]; or stress can be stretching, as an example, stretching a flexible membrane on which cells are attached [10].

By forcing a cell to enter a small space, one imposes its geometry. For example, Takeuchi et al. used agarose and PDMS microchambers to force E. coli cells to grow in a circular or sinusoidal shape [11], and Terenna et al. used curve PDMS microchannels to constrain growing yeast cells, which are normally straight, to grow bent in order to study the reorganization of its cytoskeleton [2]. Minc et al. achieved similar results by pushing long yeast cells into PDMS microwells, which made the cells buckle and bend [12]. This method has been used to study yeast polarization and to determine elastic modulus of the cell wall and cell turgor pressure [13]. Beyond shape changes, artificial confinement can induce cell behavior which illuminates underlying mechanisms.

For example, Faure-Andre et al. injected dendritic cells into microchannels and found that the cells recovered their integrin-independent motile behavior found in living tissues [6]. Chau et al. used a PDMS/matrigel device to study cancer metastasis by following migration and deformation of cancer cells in microchannels [14].

For more information about cell deformation you can read the section mechanical deformation and force measurement of our review about microfluidics for cell biology.

If you need to control cell shape and cell mechanical stresses in a microfluidic chip our team will be glad to work with you. Elveflow provide microfluidic flow control instrument and chip to research laboratories. The aim of Elveflow scientific team is to enable all scientific laboratories to use microfluidic in a plug and play manner.

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References

[1] . S. D. Hudson, F. R. Phelan Jr, M. D. Handler, J. T. Cabral, K. B. Migler and E. J. Amis, Appl. Phys. Lett. 85 (2004) 335.

[2]. C. R. Terenna, T. Makushok, G. Velve-Casquillas, D. Baigl, Y. Chen, M. Bornens et al., Curr. Biol. 18 (2008) 1748.

[3] . J. Meyers, J. Craig and D. J. Odde, Curr. Biol. 16 (2006) 1685.

[4] . A. Katsumi, A. W. Orr, E. Tzima and M. A. Schwartz, J. Biol. Chem. 279 (2004) 12001.

[5] . M. Chrzanowska-Wodnicka and K. Burridge, J. Cell Biol. 133 (1996) 1403.

[6]. G. Faure-Andre, P. Vargas, M. I. Yuseff, M. Heuze, J. Diaz, D. Lankar et al., Science 322 (2008) 1705.

[7]. J. M. Higgins, D. T. Eddington, S. N. Bhatia and L. Mahadevan, Proc. Natl. Acad. Sci. USA 104 (2007) 20496.

[8] . J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke et al., Biophys.

J. 88 (2005) 3689.

[9]. R. S. Carvalho, A. Bumann, C. Schwarzer, E. Scott and H. K. Yen, Eur. J. Orthodontics 18 (1996) 227.

[10] . J. Zhuang, K. A. Yamada, J. E. Saffitz and A. G. Kleber, Circ. Res. 87 (2000) 316.

[11] S. Takeuchi, W. R. DiLuzio, D. B. Weibel and G. M. Whitesides, Nano Lett. 5 (2005) 1819.

[12]N. Minc, S. V. Bratman, R. Basu and F. Chang, Curr. Biol. 19 (2009) 83.

[13]. N. Minc, A. Boudaoud and F. Chang, Curr. Biol. 19 (2009) 1096.

[14]. K. C. Chaw, M. Manimaran, E. H. Tay and S. Swaminathan, Lab Chip 7 (2007) 1041.