Control of Cell Adhesion by Mechanical Reinforcement of Soft Polyelectrolyte Films with Nanoparticles Stephan Schmidt, †,‡ Narayanan Madaboosi, †,‡ Katja Uhlig, † Dorothee Kö hler, ‡ Andre ́ Skirtach, ‡,§,∥ Claus Duschl, † Helmuth Mö hwald, ‡ and Dmitry V. Volodkin* ,† † Fraunhofer Institut fü r Biomedizinische Technik, Am Mü hlenberg 13, 14476 Potsdam-Golm, Germany ‡ Max Planck Institut fü r Kolloid und Grenzflä chenforschung, Am Mü hlenberg 1, 14476 Potsdam-Golm, Germany § Department Molecular Biotechology, University of Ghent, Coupure Links 653, B-9000 Ghent, Belgium ∥ Center for Nano- and Biophotonics, University of Ghent, Sint-Pietersnieuwstraat 41, B-9000 Ghent, Belgium * S Supporting Information ABSTRACT: Chemical cross-linking is the standard approach to tune the mechanical properties of polymer coatings for cell culture applications. Here we show that the elastic modulus of highly swollen polyelectrolyte films composed of poly(L-lysine) (PLL) and hyaluronic acid (HA) can be changed by more than 1 order of magnitude by addition of gold nanoparticles (AuNPs) in a one-step procedure. This hydrogel-nanoparticle architecture has great potential as a platform for advanced cell engineering application, for example remote release of drugs. As a first step toward utilization of such films for biomedical applications we identify the most favorable polymer/nanoparticle composition for optimized cell adhesion on the films. Using atomic force microscopy (AFM) we determine the following surface parameters that are relevant for cell adhesion, i.e., stiffness, roughness, and protein interactions. Optimized cell adhesion is observed for films with an elastic modulus of about 1 MPa and a surface roughness on the order of 30 nm. The analysis further shows that AuNPs are not incorporated in the HA/PLL bulk but form clusters on the film surface. Combined studies of the elastic modulus and surface topography indicate a cluster percolation threshold at a critical surface coverage above which the film stiffness drastically increases. In this context we also discuss changes in film thickness, material density and swelling ratio due to nanoparticle treatment. 1. INTRODUCTION There is a growing demand for surface coatings that allow not only the control of cellular adhesion but also the regulation of cell morphogenesis by surface mediated signaling or even remote release of drugs. 1−6 Control of the cell behavior can be achieved by adjusting chemical interactions between membrane and the synthetic surface. 7 There is also evidence that cellular signaling pathways and cell fate are affected by the mechanical environment of the cell. 8 It was found that a large range of cell parameters, such as adhesion, viability, proliferation, and motility can be controlled by the stiffness 9−11 and microscopic surface patterning 12 of the underlying film. Therefore, in view of biomedical applications, it is of great importance to be able to prepare coatings with well controlled topography and mechanical properties. With the discovery of the layer-by-layer (LbL) deposition of polyelectrolyte multilayer films, 13,14 a versatile route toward thin films has been introduced. LbL assembly can be conducted with precise control over film properties such as thickness, microscopic roughness, and surface chemistry. More recent advances showed that specific biological activities can be induced by incorporation of bioactive species in polyelectrolyte multilayers. 5,6,15−21 For biomedical applications these materials are composed of biocompatible and degradable polyelectrolytes based on carbohydrates or poly(aminoacids). One of the most prominent polyelectrolyte pairs in this context is hyaluronic acid/poly(L-lysine) (HA/PLL), which was shown to form Received: February 13, 2012 Revised: March 26, 2012 Published: April 17, 2012 Article pubs.acs.org/Langmuir © 2012 American Chemical Society 7249 dx.doi.org/10.1021/la300635z | Langmuir 2012, 28, 7249−7257