Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Embryonic and pluripotent stem cells hold great promise in generating beta-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these beta-like cells still fail to fully mirror the adult beta-cell physiology. For their proper growth and functioning, beta-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where beta-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in beta-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that beta-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the beta-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of beta-cell differentiation capacity in vitro.