_____________________________________________________________________ We generated, on titanium surfaces, self-assembledlayersofverticallyorientatedTiO2 nanotubes withdefined diameters between15 and 100 nm and show that adhesion, spreading, growth and differentiation of mesenchymal stem cells are critically dependent on the tube diameter. A spacing less than 30 nm with a maximum at 15 nm provided an effective length scale for accelerated integrin clustering / focal contact formation and

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... enhances cellular activities compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in dramatically reduced cellular activity and a high extent of programmed cell death. Thus, mesenchymal stem cells seems to be very sensitivetonano-scalemicroenvironmentsuch asalateralspacing geometryrepresenting30-50 nm of nanotube diameter as a critical borderlineforcellfate.