Surface-induced cell signaling events control actin rearrangements and motility Ian S. Miller, 1 Iseult Lynch, 2 Denis Dowling, 3 Kenneth A. Dawson, 2 William M. Gallagher 1 1 UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland 2 UCD School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland 3 UCD Advanced Manufacturing Science Research Centre, Surface Engineering Centre, University College Dublin, Belfield, Dublin 4, Ireland Received 14 September 2008; revised 11 March 2009; accepted 12 March 2009 Published online 7 July 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.32530 Abstract: Understanding the interrelationship between material surface properties and the biological response to such materials remains a fundamental scientific challenge, as well as being of considerable practical importance in medicine. Through the use of a homologous series of copolymers of increasing hydrophobicity, we aimed to illu- minate the interplay between material surface hydropho- bicity and signalling events within cells in contact with this model system. Extending previous work, we hereby unravel key pathways controlling cell motility and the for- mation of a stellate phenotype, following interaction with polymer-coated surfaces. We reveal a comparative increase in cellular motility with increasing surface hydrophilicity, conjoint with an arrest in cell cycle progression. We also show an anomalous turnover of actin within the cell as a function of changing surface hydrophobicity. Finally, we show that cyclic adenosine monophosphate may be an effector of the cellular phenotype, as its production is increased in response to changes in the surface properties. These results highlight important signaling events which control actin rearrangements and the subsequent motility and its effectors. Ó 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 493–504, 2010 Key words: copolymer; adhesion; hydrophobicity; signal- ing; actin INTRODUCTION For some years, the emphasis of biomaterials research has been strongly influenced by the concept that material-cell interactions are governed primarily by properties of the surface, along with other physi- cal forces. As a consequence, many efforts, often trial and error, have been made to tailor the physiochemi- cal surface properties of materials to promote desirable (or avoid undesirable) biological responses. 1–8 Thus, it is probably fair to say that at present there exists no overall concept of rational biomaterials science in the context of predicting cel- lular response. Given the supposed complexity of the systems, there is no clear sign that such a frame- work is viable. For example, it is surprising to note that even changing a single chemical moiety can lead to an alteration of how the cell or organism reacts to a given material, suggesting that averaged physiochemical properties are not in themselves suf- ficient to predict biological interactions. 1–3,5–7,9 How- ever, a rational understanding of the connection between the material and the biological response it elicits in a complex biological fluid remains an attractive possibility, and the present article seeks to develop this concept further. This clarification of the nature of the surface in a bi- ological environment provides one link in the overall development of a rational approach to the field. Evi- dently, we now seek to understand the relevant range of cellular responses and processes induced by contact with the ‘‘material.’’ Indeed, technology Additional Supporting Information may be found in the online version of this article. Correspondence to: W. M. Gallagher; e-mail: william. gallagher@ucd.ie Contract grant sponsors: Science Foundation Ireland (SFI RFP Spatio-temporal aspects of nanoparticle interactions with cells), The Wellcome Trust, The Health Research Board, Enterprise Ireland (Basic Research Grant and Proof of Concept), EU FP6 (NanoInteract) Ó 2009 Wiley Periodicals, Inc.