The use of controlled surface topography and flow-induced shear stress to influence renal epithelial cell function

Abstract

Physiologically-representative and well-controlled in vitro models of human tissue provide a means to safely, accurately, and rapidly develop therapies for disease. Current in vitro models do not possess appropriate levels of cell function, resulting in an inaccurate representation of in vivo physiology. Mechanical parameters, such as sub-micron topography and flow-induced shear stress (FSS), influence cell functions such as alignment, migration, differentiation and phenotypic expression. Combining, and independently controlling, biomaterial surface topography and FSS in a cell culture device would provide a means to control cell function resulting in more physiologically-representative in vitro models of human tissue. Here we develop the Microscale Tissue Modeling Device (MTMD) which couples a topographically-patterned substrate with a microfluidic chamber to control both topographic and FSS cues to cells. Cells from the human renal proximal tubule cell line HK-2 were cultured in the MTMD and exposed to topographic patterns and several levels of FSS simultaneously. Results show that the biomaterial property of surface topography and FSS work in concert to elicit cell alignment and influence tight junction (TJ) formation, with topography enhancing cell response to FSS. By administering independently-controlled mechanical parameters to cell populations, the MTMD creates a more realistic in vitro model of human renal tissue.