Poly(ethylene glycol) as a sensitive regulator of cell survival fate on polymeric biomaterials: the interplay of cell adhesion and pro-oxidant signaling mechanisms

Abstract

Poly(ethylene glycol) (PEG) is one of the most widely used compounds across a variety of platforms and is increasingly found in medical applications. Polycarbonates containing varying mol% of PEG (M_w 1000) were used to probe the effects of PEG on cell adhesion, proliferation, spreading, and survival. Two contrasting PEG-mediated cell signaling elements affected these cellular behaviors: (i) integrin α5 receptor mediated cellular focal adhesions to the biomaterial surface and (ii) modulation of cellular redox and apoptosis through generation of reactive oxygen species (ROS). At lower PEG_1k mol% (5% and 8%) cell attachment and spreading decreased concomitantly due to ROS, whereas at the higher PEG_1k mol% studied (10% and 20%) an unusual super-adhesive behavior was observed. At higher PEG_1k mol% cells exhibited greatly enhanced spreading, which was confirmed through immunolocalization of integrin α5 receptors and enhanced mRNA expression of the integrin α5 gene. These cellular responses on higher PEG_1k mol% co-polymers were sufficient to overcome the ROS-driven effects on caspase activation and cell shrinkage, which dominated at lower PEG_1k mol%. These studies elucidate PEG-mediated cellular signaling with the implication that the adhesion and apoptotic activity of PEG-rich materials can be sensitively controlled by anti-oxidant addition. Moreover, this study shows that biomaterials can drive the cell fate in opposing directions through concurrent property changes.