Cell strain energy costs of active control of contractility

Cell mechanosensing is implicated in the control of a broad range of cell behaviours, with cytoskeletal contractility a key component. Experimentally, it is observed that the contractility of the cell responds to increasing substrate stiffness, showing increased contractile force and changing the distribution of cytoskeletal elements. Here we show using a theoretical model of active cell contractility that upregulation of contractility need not be energetically expensive, especially when combined with changes in adhesion and contractile distribution. Indeed, we show that a feedback mechanism based on maintenance of strain energy would require an upregulation in contractile pressure on all but the softest substrates. We consider both the commonly reported substrate strain energy and active work done. We demonstrate substrate strain energy would select for the observed clustering of cell adhesions on stiffer substrates which also enable an upregulation of total contractile pressure; while localisation of contractility has the greatest impact on the internal work.