In this paper, Dr Biggs and his team collaborated with Prof Shalom Wind, at Columbia University to investigate the functional response of mesenchymal stem cells to the physicomechanical properties of their environment, factors which play key roles in multiple cell processes such as adhesion and differentiation. Recent studies indicate that stem cells undergo differentiation to a specific tissue lineage when grown on a substrate that matches the rigidity of that tissue, yet although tissues are associated with a set range of values for bulk rigidity, at the sub-cellular level, and particularly at the micro- and nanoscale levels, tissues are comprised of multiple elements (such as fibres, cells, crystals) with widely differing rigidity.
The paper reports on the use of electron-beam patterning to alter the rigidity of an elastomeric substrate at discrete regions, thereby enabling the development of a new class of 2D substrates possessing patterned features of controlled rigidity, ranging from the micron to the nanoscale level. Electron-beam patterning allowed for the fabrication of devices with nanoscale resolution, and it was shown for the first time that that direct-write electron-beam exposure can significantly alter the rigidity of an elastomeric material. The response of human mesenchymal stem cells to electron-beam patterned substrates was subsequently investigated and significant modulation of focal adhesion formation and osteochondral lineage commitment as a function of both feature diameter and rigidity was identified.