Julien Gautrot: Cell Biomaterials Interfaces






12th May 2015
Invited talk at the Biomaterials Seminar Glasgow
Julien Gautrot, School of Engineering and Materials Science, Queen Mary, University of London

 Julien gave a roundup on why physical influences are important to consider, across a rage of lengthscales from nano, defining adhesions, micro where the cell shape can be defined, and mill++ where size and shape affects how tissues and organs form and are defined. He then went on to talk about the reasons that the polymer brushes developed to reliably keep surfaces protein and thus cell adhesion free (Biomaterials 2010). These were used in the nice paper with Fiona Watt on ceratocyte differentiation in dependence on island size (NCB 2010), where F-/g-actin ratio was affected by island size and correlated with differentiation, mediated by serum response factor signalling. The same technology was used to define larger islands, with holes with increasing size, where at 20µm these were ignored, whereas that were 60µm or above would keep open. The cells on these islands showed a change in position depending on their differentiation state - initially they adhere to the surface with integrin adhesions dominating, this then gets down and cadherin cell-cell adhesion are upregulated. With this the mechanical balance of physical forces leads to a repositioning of the differentiated cells towards the middle of the island (Biomaterials 2012). Then Julien went on to describe how he developed a thiolene linker technology that allows to generate haptotactic gradients, to immobilise RGD on surfaces. These were used to develop an alternative to the scratch wound assay widely used to look at cell sheet repair and migration (Acta Biomat. 2014). Combining the nice surface chemistry developed was combined with a natural lithography approach developed by Duncan Sutherland (iNano, Aarhus, DK) to allow to control substrate adhesions with nanometric resolution (ACS Nano 2014). In the last minutes he discussed how environmental mechanics may work to control cell fate. This is based on the nice intellectual 'battle' started by by a robust challenge to the finding by Engler et al. in 2004 that MSC differentiation could be influenced by extracellular matrix stiffness. In their paper the group of Julien and Fiona Watt showed (NMat 2012) that this may have been due to substrate tethering rather than apparent substrate stiffness. (Last year Engler's group replied in an interesting paper in NMat 2014). From his ongoing work on measuring the mechanics that the cells do experience, the story is to be continued, and the answer not yet fully determined...