Abstract
Cells are continuously sensing their microenvironment and subsequently respond to different physicochemical cues by the activation or inhibition of different signaling pathways. To study a very complex cellular response, it is necessary to diminish background environmental influences and highlight the particular event. However, surface-driven nonspecific interactions of the abundant biomolecules from the environment influence the targeted cell response significantly. Yes-associated protein (YAP) translocation may serve as a marker of human hepatocellular carcinoma (Huh7) cell responses to the extracellular matrix and surface-mediated stresses. Here, we propose a platform of tunable functionable antifouling poly(carboxybetain) (pCB)-based brushes to achieve a molecularly clean background for studying arginine, glycine, and aspartic acid (RGD)-induced YAP-connected mechanotransduction. Using two different sets of RGD-functionalized zwitterionic antifouling coatings with varying compositions of the antifouling layer, a clear correlation of YAP distribution with RGD functionalization concentrations was observed. On the other hand, commonly used surface passivation by the oligo(ethylene glycol)-based self-assembled monolayer (SAM) shows no potential to induce dependency of the YAP distribution on RGD concentrations. The results indicate that the antifouling background is a crucial component of surface-based cellular response studies, and pCB-based zwitterionic antifouling brush architectures may serve as a potential next-generation easily functionable surface platform for the monitoring and quantification of cellular processes.
Highlights
Living cells are continuously sensing their microenvironment and adapt to different physicochemical events during their lifetime [1,2]
The subcellular location of Yes-associated protein (YAP) is influenced by the substrate rigidity and topography of the surface [11,12,13], cell geometry and morphology driven by the surface characteristics and surrounding conditions [14,15,16], or the density of the population and contact among the cells [17,18]
We demonstrate a smooth approach to control the level of extracellular mechanical stress using the cell adhesion-promoting RGD-functionalized antifouling polymer brushes
Summary
Living cells are continuously sensing their microenvironment and adapt to different physicochemical events during their lifetime [1,2]. Mechanotransduction, defined as the conversion of mechanical cues into biochemical signals, leads to cellular responses important for cell function in health (i.e., growth and differentiation) and diseases (i.e., cancer malignant progression) [4]. Among these mechanosensing processes, integrin mediates cell adhesion, leads to the cell response by recruiting intracellular multiprotein assemblies such as F-actin [5], or influences the Yes-associated protein (YAP) location [6]. The regulation of YAP is a complex process, which encompasses several different factors, such as cell density and polarity, mechanical stress, cellular energy status, etc. The subcellular location of YAP is influenced by the substrate rigidity and topography of the surface [11,12,13], cell geometry and morphology driven by the surface characteristics and surrounding conditions [14,15,16], or the density of the population and contact among the cells [17,18]
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