Fate and function of anchorage-dependent cells are known to depend on multiple environmental cues, including those of mechanical origin. Cells probe external mechanical cues through cellular adhesions, such as focal adhesions and adherens junctions, which act as sensitive mechanosensors. Previous progress in the understanding of cellular mechanosensitivity can largely be attributed to the availability of linker-functionalized polymeric gels of adjustable stiffness, which mimic extracellular matrix (ECM) conditions. However, such ECM mimetics are limited in their ability to replicate the remarkable plasticity and dynamics found at cell-cell junctions. To overcome this shortcoming, here we introduce the cadherin functionalized polymer gel-supported lipid bilayer (PGSB) as an improved cell-cell interface mimetic. Its key features include: (i) the dynamic assembly of linker molecules into linker clusters at cell adhesions, enabling cell spreading and migration, and (ii) the ability to alter substrate stiffness by changing the composition of the underlying polymer gel. Experimental findings are presented which show that adherent cells on PGSB substrates of varying gel stiffness exhibit markedly different global properties of cellular mechanosensitivity (i.e., cell area, migration speed, and cytoskeleton organization). Furthermore, cadherin clusters underneath plated cells show long-range lateral mobility with remarkable similarity to the dynamics of cell-cell junctions in cell clusters. These results illustrate that the linker functionalized PGSB is a promising cell surface-mimicking substrate for the analysis of cellular mechanosensitivity.

Examining cell migration and cell junction dynamics using polymer gel-supported lipid bilayers

253rd National Meeting (2017)

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