It is time to crowd your cell culture media - Physicochemical considerations with biological consequences

In vivo, the interior and exterior of cells is populated by various macromolecules that create an extremely crowded milieu. Yet again, in vitro eukaryotic cell culture is conducted in dilute culture media that hardly imitate the native tissue density. Herein, the concept of macromolecular crowding is discussed in both intracellular and extracellular context. Particular emphasis is given on how the physicochemical properties of the crowding molecules govern and determine kinetics, equilibria and mechanism of action of biochemical and biological reactions, processes and functions. It is evidenced that we are still at the beginning of appreciating, let alone effectively implementing, the potential of macromolecular crowding in permanently differentiated and stem cell culture systems.