A system to impose prescribed homogenous strains on cultured cells

There is presently significant interest in cellular responses to physical f orces, and numerous devices have been developed to apply stretch to culture d cells. Many of the early devices were limited by the heterogeneity of def ormation of cells in different locations and by the high degree of anisotro py at a particular location. We have therefore developed a system to impose cyclic, large-strain, homogeneous stretch on a multiwell surface-treated s ilicone elastomer substrate plated with pulmonary epithelial cells. The pne umatically driven mechanism consists of four plates each with a clamp to fi x one edge of the cruciform elastomer substrate. Four linear bearings set a t predetermined angles between the plates ensure a constant ratio of princi pal strains throughout the stretch cycle. We present the design of the devi ce and membrane shape, the surface modifications of the membrane to promote cell adhesion, predicted and experimental measurements of the strain field , and new data using cultured airway epithelial cells. We present for the f irst time the relationship between the magnitude of cyclic mechanical strai n and the extent of wound closure and cell spreading.