The mechanics of reversible adhesion of the gecko is investigated in terms of the attachment and detachment mechanisms of the hierarchical microstructures on its toe. At the bottom of the hierarchy, we show that a spatula pad of tiny thickness can be well absorbed onto a substrate with a large surface area and a highly constrained decohesion process zone, both of which are beneficial for robust attachment. With different peeling angles, the peeling strength of a spatula pad for attachment can be 10 times larger than that for detachment. At the intermediate level of hierarchy, we show that a seta can achieve a stress level similar to that in the spatula pad by uniformly distributing adhesion forces; as a consequence, the 10 times difference in the peel-off force of a single spatula pad for attachment and detachment is magnified up to a 100 times difference in adhesion energy at the level of seta. At the top of the hierarchy, the attachment process of a gecko toe is modelled as a pad under displacement-controlled pulling, leading to an adhesive force much larger than the gecko's body weight, while the associated detachment process is modelled as a pad under peeling, resulting in a negligible peel-off force. The present work reveals, in a more systematic way than previous studies in the literature, that the hierarchical microstructures on the gecko's toe can indeed provide the gecko with robust adhesion for attachment and reversible adhesion for easy detachment at the same time.

Although Erk kinase has been recently reported to function in the DNA damage response, the mechanism governing this process is unknown. We report here that hydroxyurea (HU) activates Erk via MEK1, a process that is sensitized by a constitutively active MEK1 (MEK1Q56P) and attenuated by a dominant-negative MEK1 (MEK1K97M). While ectopic MEK1Q56P sensitized HU-induced S-phase arrest, inhibition of Erk activation via U0126, PD98059, and MEK1K97M attenuated the arrest, and thereby enhanced cells to HU-induced toxicity. Taken together, we demonstrate an important contribution of Erk to the activation of the S-phase DNA damage checkpoint. This can be attributed to Erk's regulatory role in modulating ATR function. Inhibition of Erk activation with U0126/PD98059 and MEK1K97M substantially reduced HU-induced ATR nuclear foci, leading to a dramatic reduction of cH2AX and its nuclear foci. Reduction of MEK1 function by a small interference RNA (siRNA) MEK1 and ectopic MEK1K97M significantly decreased HU-induced cH2AX. Conversely, ectopic MEK1Q56P enhanced cH2AX foci. Furthermore, immunofluorescent and cell fractioning experiments revealed cytosolic and nuclear localization of ATR. HU treatment caused the redistribution of ATR from the cytosol to the nucleus, a process that is inhibited by U0126. Collectively, we show that Erk kinase modulates HU-initiated DNA damage response by regulating ATR function.

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