organization in septic monolayers. Furthermore, our data suggest that the proteins in the tight junction complex are more weakly associated with the cytoskeleton in monolayers composed of cells from septic animals. These data highlight a need for understand- ing how sepsis alters the tight junction, the actin cytoskeleton, and the molecules that regulate barrier properties. Supporting Information Figure S1 Stretch to 25% DSA induced significant phosphorylation of JNK in sham cells at 60 minutes compared to unstretched (NS) (*, p,0.05), but did not induce JNK phosphorylation at either time point. Stretch to 25% DSA for 10 minutes induced significant ERK phosphor- ylation in both sham and 2CLP monolayers compared to unstretched sham only (*, p,0.05), or to both unstretched sham and unstretched 2CLP (*,#, p,0.05). At 60 minutes of stretch, ERK phosphorylation had subsided in 2CLP monolayers, and was no longer significant from any other time point, while ERK phosphorylation in sham monolayers was still significantly elevated above unstretched sham. (mean 6 SE, N$6 isolations). (TIFF) Figure S2 Inhibition of MAPk signaling (JNK-SP600125 20 mM, ERK-U0126 10 mM) did not prevent stretch- induced permeability increases in 2CLP monolayers when stretched (ST) to 25% DSA. ERK inhibition prevented References 1. Zambon M, Vincent JL (2008) Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest 133: 1120–1127. 2. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, et al. (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353: 1685–1693. 3. Wheeler AP, Bernard GR (2007) Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet 369: 1553–1564. 4. Wolthuis EK, Vlaar AP, Choi G, Roelofs JJ, Juffermans NP, et al. 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