A disruption of epithelial and endothelial barrier function is a typical pathological change in acute sepsis. Two major mechanisms have to be considered responsible for barrier breakdown. Signals generated by the deregulated and overreacting immune system, as well as signals or activities from pathogenic bacteria and fungi directly interacting with epithelial or endothelial cells are assumed to contribute to barrier breakdown. Here we want to specifically analyze inactivation of the apical junctional complex (AJC) and the role of junction-associated adaptor proteins with NACos (nuclear and adhesion complex) function (e.g. catenins, ZO-proteins) during sepsis. Both pathways are interconnected and provide interesting targets to treat organ failure in sepsis. Microfluidically supported biochips will be used to study the cross-communication of human gut and liver tissue models with respect to the impact of cytokine-mediated regulation of tight and adherens junction protein function in the breakdown of endothelial and epithelial barrier and subsequent hepatocellular dysfunction.