Circadian clocks are time-keeping mechanisms used by cells to maintain our daily 24-hour rhythms, and they drive the periodic expression of genes that control physiology, metabolism and behaviour. Having previously reported that clock gene expression is dependent on correct cell–matrix interactions and, further, that extracellular matrix stiffness is a regulator of the mammary epithelial circadian clock, Qing-Jun Meng, Charles Streuli and colleagues now extend their analysis to other tissues and cell types (Williams et al., 2018). The authors show that mammary gland, lung and epidermal epithelial cells have strong circadian clocks within a mechanically soft 3D microenvironment compared with a stiff 2D environment; by contrast, stromal fibroblastic cells isolated from the same tissues show the opposite response – enhanced oscillations in stiff environments. Using RNA analysis, the authors also find that, in epithelial cells, expression of a subset of clock genes and their regulators are elevated in soft 3D microenvironments compared with stiff microenvironments, and that the same genes are inversely controlled in fibroblasts isolated from the same tissues. This Short Report, therefore, reveals an inverse relationship between epithelial and fibroblastic circadian clocks in their responses to the mechano-matrix environment.