Cyclic biaxial strain affects U937 macrophage-like morphology and enzymatic activities

As monocytes migrate to the site of a foreign body and differentiate into mature monocyte-derived macrophages (MDMs), the cells undergo a morphological transformation that involves mechanical stimulation via membrane stretch. Because the site of many cardiovascular implant devices includes substrates that are also undergoing mechanical change, it is of interest to assess the effect of such dynamic conditions on cellular-biomaterial responses. This study investigated the influence of cyclic (0.25 Hz) biaxial strain (maximum 10% amplitude) on human U937 macrophage-like cells cultured on a flexible siloxane membrane. Cell attachment was unaffected by the strain but total protein levels were significantly higher in stimulated cells. Intracellular esterase and released acid phosphatase activities were elevated by dynamic loading in addition to a strain-induced increase of monocyte-specific esterase protein as demonstrated by immunoblotting analysis. The morphology of static cells changed with cyclic strain from a round cell shape to an irregular, spread phenotype with a progressive reorganization of filamentous actin. The focal adhesion protein vinculin showed distinct reorganization in structure going from a well-defined arrangement in static cells to a diffuse staining pattern in mechano-stimulated cells. This study has demonstrated that U937 cells respond to cyclic deformation with an augmentation of select enzymatic activities that have been identified as being important in polymer biodegradation processes, as well as morphological changes, which may be characteristic of mechanical stress-induced cell activation.