Investigating how cell surface mechanics gates intracellular signalling to instruct cell fate choice

In order to perform their function (differentiation or self-renewal), stem cells need to receive a signal.

Historically, the focus was put on the importance of soluble factor signals, but it is nowadays widely appreciated that the mechanical environment of stem cells plays a role in their function and affects soluble factor signalling. This is for example illustrated in oligodendrocyte progenitor cells (OPCs).

With ageing, due to alterations in stiffness of the extracellular matrix (ECM) in the brain, OPCs lose their function, becoming unable to give rise to oligodendrocytes, a cell type which supports neurons.

Using human pluripotent stem cells (hPSCs) and OPCs as systems, I will investigate the mechanism which underlies the effect that various properties of the mechanical environment (stiffness, stability) have on interpretation of soluble factor signalling (intracellular signalling) in stem cells and on their function.

In response to different properties of the mechanical environment, I will monitor changes in membrane tension, receptors binding ECM and signalling platforms clustering soluble factor receptors.

Understanding of how cell surface mechanics gates intracellular signalling in a basic model such as the hPSCs can further be applied to OPCs to shed light on how and why OPCs lose function as they age.