Mechanosensing at the nanoscale: the influence of thermoplastic nanostructures on neural cells

It is well established that the behavior of neural cells is influenced by geometrical patterns in the micrometric and sub-micrometric range. Here we present two different types of periodical patterns in the nanometric range (i.e. with a typical features having a lateral size ≤ 100 nm) and their impact on cell contact guidance. In the first case, hierarchical periodic nano-rippled structure (i.e. nano-ripples) made by ion-bombardment technique were replicated on top of polyethylene terephtalate (PET) films. We demonstrated that Schwann cells actively interact with these nanorippled surfaces, showing perpendicular contact guidance and improved adhesion and proliferation with respect to standard flat substrates. The second type of scaffolds here presented consist in cyclic-olefin-copolymer (COC) nanogratings with periodicity (down to 200nm -50% duty cycle), obtained by hot embossing from photoresist molds fabricated by interference lithography. In this case, we coupled the substrates with the PC12 neuronal cell line and measured the neurite alignment and focal adhesion (FA) morphometric parameters. We show optimal contact guidance in the case of periodicity > 400nm, while a progressive degradation of polarized alignment appears by further decreasingthe grating lateral dimensions, correlating with FA shaping. These results set for the first time a lower limit in grating periodicity for effective neurite contact guidance. Altogether thesestudies provide interesting elements for regenerative medicine applications and for developing artificial neural interfaces.