The Final Morning at the Mechanobiology Meeting

After the banquet, there was one last morning of scientific sessions.  It started with thanking those that made the meeting happen.  One of the organizers, Linda Kenney noted that over 30% of the speakers at the meeting were women, and encouraged others to strive to do the same when they plan meetings.   This was followed by an action packed morning session.

Xavier Trepat from IBEC, showed some very interesting studies to understand mechanisms of how cancer cells migrate out of tumors. Using tumor cells of epithelial origin (A341 cells) and from clinical samples of lung cancers that these cells could indeed bind using cell-cell adhesions mediated by E cadherin and N cadherin. To demonstrate that these two cadherins can form heterotypic adhesions they presented different cadherin (E,N,P) on magnetic beads to the cells. A magnetic field was applied for a minute and assayed how the percentage of beads bound to the cell. Here they saw that N-cad- Ecad adhesions were formed. These adhesions between cancer cells and CAFs(cancer activated fibroblasts) actually assist migration where the CAFs act as the leader cell and pull the cancer cells along their path of migration. Using traction force microscopy, they also observed that the leader cell actually pulls onto the CAFs. In some interesting preliminary experiments, the Trepat group also shows that when cancer cells associate with CAF, they lead to the polarization and subsequent migration of CAF by a yet unknown mechanism.

This was followed by a somewhat related talk by Kevin Chalut from the University of Cambridge. In his lab, they have developed a different method to make hydrogels of different rigidities in a more reliable manner. Changing only the stiffness of hydrogels they show that OPC proliferation relies on soft matrices. There was a nice study on comparing pre- and post- implantation tissue with stem cells grown on soft matrices. On comparison of gene expression profile, they found that pre-implantation embryos were comparable to soft gels whereas post-implantation embryos were comparable to stem cells grown on stiffer gels. Further they went on to show that in the brain, regeneration occurs better when the matrix is softer. Using decellularized tissues, they showed that ageing matrices are more stiff and support proliferation and regeneration to a far lesser extent compared to matrices from neonatal tissues, which are softer. Wow, so this ties in with the talk suggesting that massaging prevents ageing. So get a massage today to relax all that stiffness, and perhaps maintain a softer matrix!

Final talk of the session was delivered by Shivashankar. He suggested that matrix constraints could determine the chromatin packing in the cells. This could be critical to bring together co-regulated genes on different chromosomes into gene clusters. Within these boundary conditions there could be an erasure of the genomic memory of the cells and help transform them on the genetic landscape to cells of another type. This was demonstrated by the growth of fibroblasts on fibronectin presenting rectangular substrates and for a few days lead to the crowding of cells and they began to express E-Cadherin. Finally, they propose to use nuclear features as a biomarker for several diseases in the tissue.

After this session, poster prizes were awarded. Really exciting posters, ranging from broad topics of integrins to cadherins and engineering substrates to genomic data analyses in cancer cells and to unconventional (previously annotated with very different functions!) genes expressed in cancer tissue were recognized.

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