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

    Year: 2010

    Journal: Soft Matter, 2010, 6, 5196-5205, 20120104

    Authors: Sung H-J ‡§ 1, Luk A ‡ 1 2, Murthy NS 1, Liu E 2, Jois M 1, Joy A 1, Bushman J 1, Moghe PV 2 3, Kohn J *1

    Last authors: Joachim Kohn

    Organizations: 1 The New Jersey Center for Biomaterials, 145 Bevier Road, Rm 101, Piscataway, NJ 08854, USA. E-mail: kohn@biology.rutgers.edu; Tel: +1 732-445-0488 2 Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA 3 Department of Chemical & Biochemical Engineering, Rutgers University, Piscataway, New Jersey 08854, USA

    Country: USA, US, United States, United States of America, America

    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 (Mw 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 PEG1k mol% (5% and 8%) cell attachment and spreading decreased concomitantly due to ROS, whereas at the higher PEG1k mol% studied (10% and 20%) an unusual super-adhesive behavior was observed. At higher PEG1k 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 PEG1k mol% co-polymers were sufficient to overcome the ROS-driven effects on caspase activation and cell shrinkage, which dominated at lower PEG1k 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.