Nano-topography: Quicksand for cell cycle progression?

Abstract The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells. Graphical abstract Nano-topography influences cell mechanotransduction, by inhibiting stress fiber, formation. The lack of stress fibers blocks the transmission of out-to-inside force from, adhesion points to actin cytoskeleton and, consequently, the achievement of the critical, tensional homeostasis, which is required for RhoA activation and RhoA-dependent, suppression of p21 levels and cell cycle progression. Unlabelled Image [ABSTRACT FROM AUTHOR]