Mechano-transduction was studied in wildtype and focal adhesion (FA) protein-deficient mouse embryonic fibroblasts (MEFs). Using a cell stretcher, we determined the effect of stretch on cell morphology, apoptosis, and phosphorylation of ERK(1/2). After 20% cyclic, uniaxial stretch, FA-deficient MEFs showed morphological changes and levels of apoptosis of the order: focal adhesion kinase > p130Cas > vinculin compared to wildtype cells. ERK(1/2) phosphorylation peaked in wildtype cells at around 10 min, and in all FA-deficient cells at around 5 min. The relative change in strain energy of FA-deficient cells compared to wildtype cells was of the order: vinculin > FAK > p130Cas. Taken together, FAK and p130Cas are more important in the stretch-mediated downstream signaling and cell survival pathway, while vinculin is more critical in maintaining cell contractility. (C) 2011 Elsevier Inc. All rights reserved.