The mechanical properties of tissues play a crucial role in tissue function and disease. However, investigation of tissue mechanics requires special needs for the underlying culture scaffold. Organotypic tissue preservation and good adhesion of the tissue explant to the substrate are prerequisites. As we have shown previously, nanostructured TiO2 substrates are ideal scaffolds to achieve these goals and adult neuronal tissues such as the retina can be long-term cultured for at least 2 weeks . Here we present that these substrates can be employed as vibrating reed to investigate the mechanical properties of adult mammalian retinae at the nanometer, viz. protein level. Within a self-designed mechanical spectroscopy setup, the reed with the retina on top is excited to perform free damped oscillations. The detected oscillation parameters represent a fingerprint of the frequency-dependent mechanical tissue properties that are derived in combination with sandwich beam analysis and finite element calculations . We found that the Young’s modulus of the retina is of the order of a few GPa, much higher than values obtained from experiments in which tissue response is investigated on micrometer length scales. In our study, polymers and proteins on the photoreceptor side of the retina in contact with the nanostructured reed are stretched and compressed during vibration of the underlying scaffold and the acting intramolecular forces are probed at the protein level. In fact, the Young’s moduli of proteins from serum – a major component of the used tissue culture medium – are about 16 times higher compared to the modulus of the TiO2 nanostructure when probed at the nanoscale (38 GPa vs. 2 GPa). To this end, our mechanical spectroscopy approach offers new perspectives in probing mechanical response of individual proteins within the tissue for studying tissue mechanics, diseases and the effect of drugs.
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 S.M. Rahman, A. Reichenbach, M. Zink, S. Mayr. Soft Matter 12, 3431 – 3441 (2016)