Phagocyte interaction with biomaterials plays an important role in inflammatory reactions. Numerous reports have shown that phagocyte behaviour at interfaces is strongly influenced by the nature and conformation of adsorbed biomolecules, which reflects, in an indirect way, the physico-chemical properties of underlying surfaces. Cell-surface interactions were thus thought to be governed by recognition events between membrane receptors and specific sites exposed by biomolecules. More recently, a growing number of reports have demonstrated that cells are also strongly influenced by physical or geometrical features such as surface rigidity or roughness and ligand topography. Here we review recent evidence supporting this concept and we describe recently disclosed cell dynamic properties that might be relevant to this phenomenon. Cell membrane movements at interfaces are expected to generate forces and deformations, and these phenomena are, in turn, expected to trigger or modulate signaling cascades through a number of processes including force-induced conformational change of membrane receptors, and alterations of in-plane movements of membrane molecules. It is suggested that a prerequisite to understanding cell behaviour at interfaces is to record all early molecular events triggered by membrane-to-surface approach and define cell decisions. (C) Koninklijke Brill NV, Leiden, 2010