Prabhas Moghe: Parsing cellular fate-switching mechanotriggers using high content imaging

2nd of April 2015, Chichley Hall




Prabhas Moghe started off giving a short history of his engagement with cell mechanobiology, before discussing in detail a very interesting paper (in late stages of preparation) on differences in nuclear organisation between mesenchymal stem cells differentiating to become adipose (fat), muscle cells, or neurons. 

Initially working towards liver cell tissue engineering Prabhas looked at double sided interfaces (Moghe et al. 1997 J Tissue Eng.). He then moved on to study how pit size and cell/tissue organisation changed mechanical signalling, mediated in parts through ß1-integrins (Ranucci et al. 2001). This was followed by work on the influence of scaffold/substrate structure on human embryonic stem cells. Here the ES cells differentiation was found to be influenced by scaffold geometry (Carlson et al. FASEBJ 2012). In more recent work his group looked into dynamic interfaces and how ligand concentration regulates cell adhesion and speed (Sharma et al. Small 2011). He then gave a background to his groups paper on high content image analysis, which resulted in a means to assess stem cell fate, by taking images of the cytoskeleton, deriving 100s of mathematical descriptors for these cells, and correlating this data to their fate. This method proved so reliable that a cells presumed fate could be derived from its cytoskeleton. Taking this approach a lot further he described how the differences in stem cell fate also affect the nucleus of a cell. It has been shown that changes in the state of a stem cell that is being lead to differentiation (using hormones, growth factors, substrate features and properties) will lead to changes in the structure of the chromatin. These changes can be picked up by a high content imaging approach, but only if super resolution imaging is applied, as the features picked up by the parsing algorithms in stem cells in different states are very small. His vision is that this groundbreaking method will enable high content screening of stem cells reaction to materials, and underpin a systems biology like approach to stem cell differentiation, and their translation.



This talk was part of a workshop on "Cell Mechanobiology" organised by Rene de Borst, which took place April 1st and 2nd 2015, with support by the Royal Society at Chicheley Hall. for the programme details see: 
http://bio-mat-sketches-mor.blogspot.co.uk/2015/04/cell-mechanobiology-workshop-1st-2nd.html