Cells not only sense and respond to soluble stimuli, but also receive various cues from the physical extracellular environment. Stimuli such as changes in substrate elasticity and extracellular matrix (ECM) composition have been shown to influence mesenchymal stem cell (MSC) fate determination. On page , Justin Cooper-White and colleagues now show that the spatial arrangement of cell adhesion ligands also affects MSC behaviour. Using adhesive substrates containing arginine-glycine-aspartate peptides tethered to self-assembled polymers of defined spacing, they show that an increase in the lateral spacing between peptides (from 34 or 44 nm to 50 or 62 nm) results in morphological changes. The cells become less well-spread, extend multiple filopodia and display a disorganised actin cytoskeleton. Closely spaced peptides also induce the formation of larger, fully mature focal adhesions, whereas nascent adhesions are more commonly found when the peptides are spaced further apart. A greater distance between adhesive ligands also results in a higher migration rate, and, depending on the spacing between peptides, they can induce opposing differentiation programmes. Together, these observations not only indicate that the lateral spacing of adhesion peptides can influence stem cell behaviour but also highlight a new aspect of the cellular environment that can be exploited for tissue engineering.
