Bacterial engineered living materials modulate mechanosignaling in mammalian cells

Abstract

Engineered living materials (ELMs) are gaining momentum for biomedical applications as self-replenishing drug depots, smart wound dressings, or as wearable sensors. Current studies on ELM-host interaction are mainly limited to the exchange of biochemical cues between ELMs and surrounding cells and tissues. Here we show that the genetically programmed mechanical properties of ELMs modulate mechanosignaling pathways in mammalian cells cultivated onto the living materials. To this aim, we genetically modulated curli fiber production in E. coli and analyzed the impact on the mechanical properties of the resulting ELMs. The living materials were used as matrix for the cultivation of mammalian cells engineered with a fluorescent reporter to indicate the activation of the mechano-responsive Hippo signaling pathway. We demonstrate that different genetically programmed ELM compositions translated into differential regulation of mechanosignaling in mammalian cells. These findings provide the perspective of using ELMs as extracellular matrix with genetically programmable mechanics for mammalian cells while also highlighting the need to consider the mechanical properties of therapeutic ELMs when assessing interaction with surrounding tissues.