7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
Employing Nanostructured Scaffolds for Long-Term Adult Tissue Culture and Investigation of Tissue Mechanics at the Nanoscale
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Tissue properties such as morphology, organization of cells and the extracellular matrix, as well as the distribution of mechanical properties can often only be accessed ex vivo. However, organotypic culture of adult tissues is still an unsolved task since tissue survival of adult fully differentiated tissues is limited to a few days in vitro. Here we show that TiO2 nanotube scaffolds with tissue-specifically tailored characteristics can serve as ideal substrates for long-term cultures of different adult tissues with high viability for at least two weeks in contrast to tissue cultures on standard PTFE membranes . Prerequisite for long-term tissue survival is an improved adhesion of the tissue to the underlying nanotube scaffold which strongly depend on the nanotube geometry in terms of tube diameter and surface roughness. Additionally, on the example of complex neural tissues such as the retina, we employ a self-designed mechanical spectroscopy setup and show that the nanotube scaffolds can be employed as vibrating reed to investigate the mechanical properties of tissue at the nanoscale, viz. protein level. Here the nanotube scaffold is clamped at one end and excited to perform free damped oscillations with the retina on top. 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 on the scale of 10 nm is of the order of a few GPa, much higher than values obtained on micrometer length scales. In our study, individual biopolymers 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. We reveal that the Young’s moduli of individual protein chains from serum – a major component of the used tissue culture medium – are about 16 times higher compared to the average modulus of the porous TiO2 nanostructure when probed at the nanoscale (38 GPa vs. 2 GPa). In fact, computer simulations of various biomolecules already demonstrated polymer stiffnesses up to 200 GPa. Since pathology and many diseases are related to changes on molecular level, e.g. during cancer progression and remodeling of the extracellular matrix, our biotechnological approach offers new perspectives in studying the relation of tissue mechanics to tumor spreading and effect of medications.