Abstract: The mechanical properties and nanotopography of the extracellular matrix have an important impact on cell phenotype. Such physical cues have been shown to regulate cell adhesion and spreading, cell motility, proliferation and differentiation in a wide range of cells, stem cells and in cancer. However, detailed mechanisms underlying mechanical and nanotopography sensing remain unclear. We are interested in developing nanoscale engineered extra-cellular matrices to study such mechanisms. In particular, we show that focal adhesions, typically regarded as essential mechanosensors, are not primary sensors of nano-scale geometry of the ECM and that the dynamics of the microscale acto-myosin network acts instead as a global sensor of the ECM nanoscale geometry. In contrast, our results demonstrate that mechanosensing occurs primarily at the nanoscale: we show that cells can directly sense the nanoscale mechanics of their environment. Indeed, we made the surprising observation that adherent cells can spread and proliferate at the surface of low viscosity liquids. We discovered that cell adhesion to such liquid substrates is mediated by the assembly of a protein nanosheet, at the interface between the two liquids (an oil and the tissue culture medium). The strength of these nanosheets, depending on parameters regulating their assembly, can sustain shear forces generated by cells during their spreading and, in turn, regulate stem cell phenotype. Our results suggest that nanoscale mechanical properties of biomaterials may dominate over bulk physical properties. This concept has important implications for the design of biomaterials in the field of regenerative medicine.
Julien Gautrot is a Professor in Biomaterials and Biointerfaces in the School of Engineering and Materials Science and Engineering at Queen Mary, University of London. His research focuses on the development of biointerfaces and microengineered biomaterials for stem cell technologies and the design of advanced cell cultured models (e.g. organ-on-chips). In particular, he developed polymer coatings, hydrogels and microfabrication platforms that are used for the formation of artificial stem cell niches and microenvironments for stem cell expansion, and the assembly of micro-tissues. He has published over 70 research articles, including in journals such as Chem. Rev., Nat. Mater., Nat. Cell Biol., Angew. Chem. Int. Ed., ACS Nano, Advanced Functional Materials and Nano Letters. In 2017, he was awarded an ERC consolidator grant. Since 2016, Dr Gautrot is the Director for Research of the Division of Bioengineering in the School of Engineering and Materials Science.
See:
http://biointerfaces.qmul.ac.uk/
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