Scheme of the molecular mechanism of bacteria/nanorough substrate interaction. (A) E. coli growing on flat gold substrates present the typical type-1 fimbriae; the two-component system Cpx pathway is inactive, thus CpxA posses a phosphatase activity which inhibits the transcription factor CpxR, resulting in a repression of degP transcription. At the same time, the promoter of the fimbrial operon is in the ON orientation. (B) The nanorough gold substrates lead to a general stress condition in E. coli, inducing a high presence of unfolded/misfolded proteins in the periplasmic space. Such misfolded proteins titrate CpxP from CpxA, whose activity shifts from phosphatase to autokinase and kinase, thus activating CpxR. This protein activates the transcription of degP which degrades unfolded proteins of the periplasmic space. Moreover, FimE switches the operon of the fimbrial promoter in the OFF orientation.