PoC - Physics of Cancer - Annual Symposium
Contributed Talk, Thursday, 17:15 – 17:30  
Microfluidic Drops as Tunable Bio-Environments

Christian Dammann, Bernd Nöding, Sarah Köster

Institute for X-Ray Physics / Courant Research Centre Nano-Spectroscopy and X-Ray Imaging, University of Göttingen, Germany

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Besides actin filaments and microtubules, intermediate filaments are a major constituent of the eukaryotic cytoskeleton. Due to the importance of the cytoskeleton for the mechanical properties of the cell, it is of high interest to understand how this complex network is built up. In a bottom up approach we focus on the assembly and network formation of vimentin intermediate filaments in vitro. The assembly of vimentin depends on the ionic strength of monovalent ions. By contrast, divalent ions act as effective cross-linkers of vimentin networks [1,2]. We are able to directly image the networks of the fluorescently tagged protein (Fig. 1b) and show that divalent ions induce compaction of these networks. For that purpose, we tailor a microfluidic device that allows for a systematic study of the effect of magnesium on vimentin networks. In this device, a series of monodisperse aqueous drops is created [3] and used as picoliter compartments for vimentin (Fig. 1a). The drops are subsequently manipulated by changing flow rates only. This manipulation process starts with the change of drop composition from drop to drop, i.e. vimentin solution is encapsulated in drops with tunable magnesium concentration. These drops are then stored in the device for long-time observations by means of constrictions in the microfluidic channel [4]. Our fluid manipulation method is designed to enable the reconstruction of the content composition of each individual drop. Possible applications of this tool are manifold, since our experimental method is not restricted to encapsulate vimentin protein solution. For example, it can be used for cell-based assays or for the study of other proteins. Due to the possibility to define different concentrations of chemicals in a large number of drops, hundreds of individual experiments are performed at the same time. This feature predestines our method also for cell-based assays in drug discovery. For instance, the response of cells to the concentration of a drug can be studied at well-defined conditions while only a few microliters of the cell solution and the drug are needed.

Fig. 1: We use the aqueous phase of a microemulsion as isolated containers for the encapsulation of vimentin intermediate filaments. This way, we study the effect of magnesium ions on vimentin networks by direct imaging of the fluorescently tagged protein in the drops.
 
[1] S. Köster, Y.-C. Lin, H. Herrmann, D. A. Weitz: Nanomechanics of Vimentin Intermediate Filament Networks, Soft Matter, 6: 1910-1914 (2010).
[2] Y.-C. Lin, N. Y. Yao, C. P. Broedersz, H. Herrmann, F. C. MacKintosh, D. A. Weitz: Origins of Elasticity in Intermediate Filament Networks, Phys. Rev. Lett., 104: 058101 (2010).
[3] S. L. Anna, N. Bontoux, H. A. Stone: Formation of Dispersions Using “Flow Focusing” in Microchannels, Appl. Phys. Lett., 82: 364 (2003).
[4] C. H. J. Schmitz, A. C. Rowat, S. Köster, D. A. Weitz: Dropspots: A Picoliter Array in a Microfluidic Device, Lab Chip, 9: 44-49 (2009).
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