Cell adhesion and migration are strongly influenced by extracellular matrix (ECM) architecture and rigidity, but little is known about the concomitant influence of such environmental signals to cell responses, especially when considering cells of similar origin and morphology, but exhibiting a normal or cancerous phenotype. Using micropatterned polydimethylsiloxane substrates (PDMS) with tuneable stiffness (500kPa, 750kPa, 2000kPa) and topography (lines, pillars or unpatterned), we systematically analyse the differential response of normal (3T3) and cancer (SaI/N) fibroblastic cells. Our results demonstrate that both cells exhibit differential morphology and motility responses to changes in substrate rigidiy and microtopography. 3T3 polarization and spreading are influenced by substrate microtopography and rigidity. The cells exhibit a persistent type of migration, which depends on the substrate anisotropy. In contrast, the dynamic of SaI/N spreading is strongly modified by the substrate topography but not by substrate rigidity. SaI/N morphology and migration seem to escape from extracellular cues: the cells exhibit uncorrelated migration trajectories and a large dispersion of their migration speed, which increases with substrate rigidity.
Abstract
Confining cells on adhesive patterns allows performing robust, weakly dispersed, statistical analysis. A priori, adhesive patterns could be efficient tools to analyze intracellular cell stress fields, in particular when patterns are used to force the geometry of the cytoskeleton. This tool could then be very helpful in deciphering the relationship between the internal architecture of the cells and the mechanical, intracellular stresses. However, the quantification of the intracellular stresses is still something delicate to perform. Here we first propose a new, very simple and original method to quantify the intracellular stresses, which directly relates the strain the cells impose on the extracellular matrix to the intracellular stress field. This method is used to analyze how confinement influences the intracellular stress field. As a result, we show that the more confined the cells are, the more stressed they will be. The influence of the geometry of the adhesive patterns on the stress patterns is also discussed.
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