Endothelium dysfunction has been associated with vascular disorders such as atherosclerosis [1], [2] and thrombosis [3], [4]. The structure and function of vascular endothelial cells are regulated by biophysical and biomechanical interactions on both the apical and basal sides. On the apical surface, hemodynamic cues, such as shear stress, control endothelial function and hemostasis [5]. While on the basement membrane, endothelial cell behavior is governed by the topography of the substrate , cellular morphology and the cytoskeleton organization [6], [7]. Electrical impedance spectroscopy provides a real time evaluation of cell migration, cell-substrate and cell-cell interaction [8]. In the study described within, we introduce a microfluidic platform that induces apical and basal-cell interactions and replicates the length scale and structure of a blood vessel, with the ability to electrically characterize endothelial cell behavior using an embedded impedance sensor. Apical cues are simulated by subjecting Human umbilical vein endothelial cells (HUVECs) to a constant shear stress of 15 dyne/cm
2 and a stepped shear condition of 20-30-50 dyne/cm
2, while, basement membrane cues are generated by seeding HUVECs into microchannels containing topographical features pertaining to the electrodes. Initial results indicate that both apical and basal cues direct. cell morphology adaptation. While cells align and stretch in the direction of flow on areas of smooth surface, they tend crowd together and arrange themselves along topographical features. Understanding how endothelial cell morphology is directed by the interaction between hydrodynamic shear stress and topographical features of electrodes within an impedance system is important in addressing these effects in impedance measurements and the need for improvements in
in vitro impedance platforms to evolve into more physiologically relevant models. Overall, these studies and technology improvements can be crucial in further comprehending normal and aberrant endothelial cell function, which can lead to new discoveries on how to treat and prevent vascular diseases.
References:
[1] P. O. Bonetti, L. O. Lerman, and A. Lerman, â??Endothelial dysfunction: A marker of atherosclerotic risk,â? Arterioscler. Thromb. Vasc. Biol., vol. 23, pp. 168â??175, 2003.
[2] P. M. Vanhoutte, â??Endothelial dysfunction and atherosclerosis,â? Eur. Heart J., vol. 18, pp. 19â??29, 1997.
[3] K. K. Wu and P. Thiagarajan, â??Role of endothelium in thrombosis and hemostasis.,â? Annu. Rev. Med., vol. 47, pp. 315â??331, 1996.
[4] J. E. Deanfield, J. P. Halcox, and T. J. Rabelink, â??Endothelial function and dysfunction: testing and clinical relevance.,â? Circulation, vol. 115, no. 10, pp. 1285â??95, Mar. 2007.
[5] J. T. Morgan, J. a Wood, N. M. Shah, M. L. Hughbanks, P. Russell, A. I. Barakat, and C. J. Murphy, â??Integration of basal topographic cues and apical shear stress in vascular endothelial cells.,â? Biomaterials, vol. 33, no. 16, pp. 4126â??35, Jun. 2012.
[6] D. E. J. Anderson and M. T. Hinds, â??Endothelial cell micropatterning: Methods, effects, and applications,â? Ann. Biomed. Eng., vol. 39, no. 9, pp. 2329â??2345, 2011.
[7] P. Lu, V. M. Weaver, and Z. Werb, â??The extracellular matrix: a dynamic niche in cancer progression.,â? J. Cell Biol., vol. 196, no. 4, pp. 395â??406, Feb. 2012.
[8] I. Giaever and C. R. Keese, â??Micromotion of mammalian cells measured electrically.,â? Proc. Natl. Acad. Sci. U. S. A., vol. 88, no. 17, pp. 7896â??900, Sep. 1991.