Cells sense the nanoscale geometry and mechanical properties of their matrix

摘要

The extra-cellular matrix (ECM) provides important cues to direct cell phenotype and stem cell fate. In particular, cell adhesion plays an important role in such sensing of the micro-environment and is modulated by physical properties of matrix, such as stiffness, topography and geometry. Our laboratory focuses on the study of such interactions and the design of biomaterials allowing the control of physical properties of the ECM. Our studies highlight that cells respond differently to nanoscale physical properties than they do to bulk properties and that the two can be designed independently. In order to control the geometry of materials at the nanoscale, we have developed patterning protocols to generate nano-patches and nano-fibres with controlled dimension and promoting cell adhesion. These platforms rely on the extreme protein resistance of some polymer brushes and the ease with which these coatings can be structure to control the geometry of protein patterns at multiple scales, from 100 nm to the millimeter scale. We find that stem cell fate is controlled by such geometry and that this behavior is mediated by changes in cell adhesion and spreading. At the nanoscale, protein recruitment dynamics (studied via live fluorescence microscopy and fluorescence recovery after photobleaching) controls adhesion formation and nanoscale sensing. Our recent studies also highlighted that cells may not feel bulk mechanical properties, at the single cell level, but rather directly sense nanoscale mechanics of the matrix. In some situations, the two may match, but this is not necessarily the case. We use self-assembly processes to control the nanoscale mechanical properties of adhesive protein layers independently of the bulk mechanical properties of the matrix. We study such properties via scanning probe microscopy and rheology and find that cell adhesion correlates with nanoscale properties rather than the bulk. This in turn controls fate decision in stem cells.