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Abstract Mechanosensitive mechanisms are often used to sense damage to tissue structure, stimulating matrix synthesis and repair. While this kind of mechanoregulatory process is well recognized in eukaryotic systems, it is not known whether such a process occurs in bacteria. InVibrio cholerae, antibiotic-induced damage to the load-bearing cell wall promotes increased signaling by the two-component system VxrAB, which stimulates cell wall synthesis. Here we show that changes in mechanical stress within the cell envelope are sufficient to stimulate VxrAB signaling in the absence of antibiotics. We applied mechanical forces to individual bacteria using three distinct loading modalities: extrusion loading within a microfluidic device, direct compression and hydrostatic pressure. In all cases, VxrAB signaling, as indicated by a fluorescent protein reporter, was increased in cells submitted to greater magnitudes of mechanical loading, hence diverse forms of mechanical stimuli activate VxrAB signaling. Reduction in cell envelope stiffness following removal of the endopeptidase ShyA led to large increases in cell envelope deformation and substantially increased VxrAB response, further supporting the responsiveness of VxrAB. Our findings demonstrate a mechanosensitive gene regulatory system in bacteria and suggest that mechanical signals may contribute to the regulation of cell wall homeostasis. 

Material manufacturing accounts for more than 25% of global carbon emissions, primarily due to the manufacture of materials used in construction, vehicles, and machines. Replacement with materials manufactured in a more sustainable manner may greatly reduce energy needs worldwide. One way to reduce the carbon impact of engineering materials is to use living organisms to manufacture and/or maintain or augment material utility – a class of materials known as Engineered Living Materials (ELMs). However, ELMs are a relatively new concept, and several challenges must be overcome before this new class of materials can see broad application. Here, we discuss one of the greatest challenges in designing ELMs that can replace the most carbon intensive engineering materials: the need to achieve sufficient load bearing capacity. 

Engineered living materials (ELMs) are an emerging class of materials that are synthesized and/or populated by living cells to achieve novel functionalities including self‐healing and sensing. Providing nutrients to living cells within an ELM over prolonged periods remains a major technical challenge that limits the service life of ELMs. Bone maintains living cells for decades by delivering nutrients through a network of nanoscale channels punctuated by microscale pores. Nutrient transfer in bone is enabled by mechanical loading experienced by the material during regular use. Herein, the geometric traits of the network of channels and pores that can be used in ELMs to allow mechanical loading to enable nutrient delivery to resident cell populations are identified in a manner seen in bone. Transport occurs when deformation in the microscale pore network exceeds the volume of the connecting channels. Computational models show that transport is enhanced at greater loading magnitudes and lower loading frequencies. The computational results are confirmed using experiments with microfluidic systems. In the findings, quantitative design principles are provided for channel‐pore networks capable of sustained delivery of nutrients to living cells within materials.