Cell-strain-energy costs of active control of contractility

Cell mechanosensing is implicated in the control of a broad range of cell behaviors, 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 the 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 preferentially select for the experimentally observed clustering of cell adhesions on stiffer substrates which effectively soften the substrate and enable an upregulation of total contractile pressure, while the localization of contractility has the greatest impact on the internal work.