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Far-from-equilibrium (FFE) conditions give rise to many unusual phenomena in nature. In contrast, synthetic shape-shifting materials typically rely on monotonic evolution between equilibrium states, limiting inherently the richness of the shape-shifting behaviors. Here we report an unanticipated shape-shifting behavior for a hydrogel that can be programmed to operate FFE-like behavior. During its temperature triggered shape-shifting event, the programmed stress induces uneven water diffusion, which pushes the hydrogel off the equilibrium based natural pathway. The resulting geometric change enhances the diffusion contrast in return, creating a self-amplifying sequence that drives the system into an FFE condition. Consequently, the hydrogel exhibits counterintuitive two opposite shape-shifting events under one single stimulation, at a speed accelerated by more than one order magnitude. Our discovery points to a future direction in creating FFE conditions to access otherwise unattainable shape-shifting behaviors, with potential implications for many engineering applications including soft robotics and medical devices.

A B S T R A C TLassa virus (LASV) causes Lassa hemorrhagic fever in humans and poses a significant threat to public health in West Africa. Current therapeutic treatments for Lassa fever are limited, making the development of novel countermeasures an urgent priority. In this study, we identified losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, from 102 screened compounds as an inhibitor of LASV infection. Losmapimod exerted its inhibitory effect against LASV after p38 MAPK down-regulation, and, interestingly, had no effect on other arenaviruses capable of causing viral hemorrhagic fever. Mechanistic studies showed that losmapimod inhibited LASV entry by affecting the stable signal peptide (SSP)-GP2 subunit interface of the LASV glycoprotein, thereby blocking pH-dependent viral fusion. As an aryl heteroaryl bis-carboxyamide derivative, losmapimod represents a novel chemical scaffold with anti-LASV activity, and it provides a new lead structure for the future development of LASV fusion inhibitors.

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