Cell Surface Mechanics Gate Embryonic Stem Cell Differentiation

Summary Cell differentiation typically occurs with concomitant shape transitions to enable specialized functions. To adopt a different shape, cells need to change the mechanical properties of their surface. However, whether cell surface mechanics control the process of differentiation has been relatively unexplored. Here we show that membrane mechanics gate exit from naive pluripotency of mouse embryonic stem cells. By measuring membrane tension during early differentiation, we find that naive stem cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. By mechanically tethering the plasma membrane to the cortex by enhancing Ezrin activity or expressing a synthetic signaling-inert linker, we demonstrate that preventing this detachment forces stem cells to retain their naive pluripotent identity. We thus identify a decrease in membrane-to-cortex attachment as a new cell-intrinsic mechanism that is essential for stem cells to exit pluripotency.
Graphical Abstract
Highlights • Early mESC differentiation is accompanied by a decrease in apparent membrane tension • Differentiating mESCs decrease their membrane-to-cortex attachment (MCA) • Development of a signaling-inert MCA (iMC) linker • MCA reduction is necessary but not sufficient for naive-to-primed transition
Bergert et al. use biophysical methods to investigate the role of cell surface mechanics during stem cell differentiation. They show that naive cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. Preventing this detachment forces cells to retain a naive pluripotent identity.