Probing Mechanosensitivity of Myoblasts on Cadherin-Functionalized Biomembrane-Mimicking Substrates

Abstract

There is a growing recognition that cells not only respond to biological signals, but also to those of mechanical nature. Cellular mechanosensing is exemplified by the cell's ability to respond to changes in substrate viscoelasticity. Traditionally, experiments about cellular substrate sensitivity were conducted on polymeric substrates with immobilized linkers. Here we present an alternative strategy based on biomembrane-mimicking cell substrates with E-cadherin cell linkers. This substrate design allows a systematic variation of viscoelastic properties by changing the number of lipid bilayers in a polymer-tethered multi-bilayer system. Importantly, individual cell linkers within this type of cell substrate are laterally mobile, thus leading to a viscous substrate behavior. In contrast, clusters of linkers, which are immobilized, cause an elasto-plastic substrate response. By using E-cadherin linkers, multi-bilayer substrates can be seen as a mimetic of a cell-cell linkage. The functionality of the multi-bilayer substrate for cellular mechnosensing studies is illustrated in terms of specific cell parameters, including cell morphology, migration speed, cytoskeletal organization, and size of cell adhesions. Furthermore, the influence of linker density on cell adhesion and spreading is discussed.