We advocate that current research on mechanotransduction in cell signaling and the general impact of mechanical materials properties on cellular functions needs to address viscous contributions. In vivo, dynamic changes in ECM composition, nonlinear elastic or fluid-like behavior of tissue are ubiquitous due to the complex mechanics of the respective constituents. Adhesion-enhancing ligands frequently bind in vivo as well as in vitro via non-covalent binding mechanisms as they are dynamically adsorbed from surrounding fluids and are actively secreted by cells to their ECM. In this process, they are constantly reorganized in the matrices and at materials interfaces. Hence, it can be assumed that
cellular processes and the interaction of cells with the surrounding ECM are influenced by dissipative phenomena, including loss in energy by molecular friction and variation of the temporal responses of the involved matrix and cell components due to a broad range of damping processes, as summarized in Fig. 3.1. However, these considerations are in contrast to the frequently used simplified systems, which exhibit linear elastic characteristics and covalently attached adhesion ligands.This chapter deals with these issues and provides examples of experimental indications that non-covalent ligand-substrate interaction can be handled as a dissipative process and leads to a control of cellular response in cell adhesion. 3.2 Viscous Properties of Cell Culture SubstratesBefore we address the impact of non-covalent ligand attachment on cell adhesion phenomena, we briefly summarize other dissipative processes within cell adhesion substrates and at the cell-material interface, which are also in place if covalent attachment schemes are applied. 3.2.1 Viscous Bulk Properties
Dissipative bulk effects are commonly elicited by viscous flow within bulk biomaterials. This process mostly arises due to the inherent viscoelastic behavior of their biopolymeric constituents. As an example, collagen networks composed of different types of collagen show different viscoelastic properties [27,39]. However, even synthetic polymer materials, frequently used as ideally elastic substrates, can exhibit viscous behavior under certain conditions [7,25]. By the choice of monomer and cross-linker concentration, polyacrylamide hydrogels with a viscoelastic response (high loss modulus G) can be fabricated as demonstrated by Cameron et al.  with significant impact on the differentiation of human mesenchymal stem cells. Similarly, Murrell et al.  varied the composition of PDMS (polydimethylsiloxane) substrates to obtain substrates with a more elastic (storage modulus G) or viscous (G) behavior, thereby achieving different degrees of coupling between the movement of epithelial cell sheets and substrate deformation. Such viscous contributions can be explained by the mechanics of
polymers and proteins as well as their linkage inside the networks, which may include both chemical as well as physical mechanisms [5,22,44].