Auer et al. developed the high-throughput 'GRABS' assay to study cell stiffness. Based on the concept that agarose provides mechanical resistance to cell elongation, GRABS measures the growth, and thus cell stiffness, of agarose-embedded cells in 96-well microplates. In a GRABS screen of 3,844 Escherichia coli deletion mutants, the 46 strongest hits — several of which were validated using a microfluidic bending assay — included not only genes with functions that are related to the cell envelope, as expected, but also 37 genes with other functions, including energy production and conversion; DNA replication, recombination and repair; and amino-acid transport and metabolism. The diversity of these functions suggests that cell stiffness is an emergent property that depends on processes beyond those that maintain the cell envelope.