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Speaker and Title Prof. Motomu Tanaka(Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University)“Quantitative biomarkers for human diseases: from collective cell order, spatio-temporal dynamics, to modeling” Dr. Natalie Munding(Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University)“Mechano-Regulation of Human Mesenchymal Stem Cells Using Stimulus Responsive Hydrogels and 3D Printed Metamaterials” Date March 28 (Tue.) , 2023 16:00-17:30 Venue Combination Room on the 5th floor, AIMR main building Abstract Quantitative biomarkers for human diseases: from collective cell order, spatio-temporal dynamics, to modeling Human diseases are associated with massive modifications of genomic, transcriptomic and proteomic signatures of the cells, which result in various pathological phenotypes. However, it is non-trivial to connect different levels of disorder to phenotypes, because a change in the expression of gene or protein (input) triggers many downstream processes and the resulting phenotypes (output). The same is true for the treatment with clinical agents. A target inhibitor often affects more than one pathyways, resulting in unknown side effects. To date, the output is mostly assessed either by the pathological image analysis or by the high throughput imaging pipline, both of which are shedding light on visual information, such as polymorphism of cells and tissues and expression of proteins by multicolor staining, of fixed, stained samples. The non-invasive phenotyping of living cells and tissues with numerical indices is a promising strategy to extract quantitative biomarkers for human diseases, because such biomarkers are fully complementary to the “static” phenotypes with no crosstalk of information. In my talk, I will introduce two types of quantitative biomarkers we developed: (A) biomarkers for the quality assessment of human corneal endothelial cells both in vitro and in vivo 1,2, and (B) biomarkers for the discrimination of clinical agents used in the treatment of acute myeloid leukemia patients 3,4. Yamamoto, A., Tanaka, H., Toda, M., Sotozono, C., Hamuro, J., Kinoshita, S., Ueno, M., and Tanaka, M. (2019). A physical biomarker of the quality of cultured corneal endothelial cells and of the long-term prognosis of corneal restoration in patients. Nature Biomedical Engineering 3, 953-960. 10.1038/s41551-019-0429-9. Ueno, M., Toda, M., Numa, K., Tanaka, H., Imai, K., Bush, J., Teramukai, S., Okumura, N., Koizumi, N., Yamamoto, A., et al. (2022). Superiority of Mature Differentiated Cultured Human Corneal Endothelial Cell Injection Therapy for Corneal Endothelial Failure. American Journal of Ophthalmology 237, 267-277. 10.1016/j.ajo.2021.11.012. Monzel, C., Becker, A.S., Saffrich, R., Wuchter, P., Eckstein, V., Ho, A.D., and Tanaka, M. (2018). Dynamic cellular phenotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents. Scientific Reports 8, 1841. 10.1038/s41598-018-19557-x. Ohta, T., Monzel, C., Becker, A.S., Ho, A.D., and Tanaka, M. (2018). Simple Physical Model Unravels Influences of Chemokine on Shape Deformation and Migration of Human Hematopoietic Stem Cells. Scientific Reports 8, 10630. 10.1038/s41598-018-28750-x. Mechano-Regulation of Human Mesenchymal Stem Cells Using Stimulus Responsive Hydrogels and 3D Printed Metamaterials Ample evidence has postulated that stem and somatic cells sense and react to both biochemical and biophysical cues from their surrounding environments. Tanaka Lab in Heidelberg (biophysical chemistry) has developed new types of materials that can mechanically stimulate and regulate single cells under interdisciplinary collaboration with clinical hematologists in Heidelberg (A.D. Ho and C. Mueller-Tidow), polymer chemists in Osaka (A. Harada and Y. Takashima), and (bio-)engineers in Karlsruhe (M. Wegener and M. Bastmeyer). In the first part, M. Tanaka will introduce the somet of our recent achievements in this field, including: (A) development of new hydrogel materials for reversible/periodic stimulation of cells 1-3, (B) mechanical manipulation of single cells in 3D printed micro-scaffolds 4, and (C) on-demand mechanical stimulation of human mesenchymal stem cells using supramolecular hydrogels with reversible host-guest crosslinks. In the second part, N. Munding will introduce an ongoing project that aims the regulation of human mesenchymal stem cell behaviors using 3D printed mechanical metamaterials. We look forward to exchanging ideas with you, hoping that we can generate a major scientific breakthrough by uniting different expertise. Yoshikawa, H.Y., Rossetti, F.F., Kaufmann, S., Kaindl, T., Madsen, J., Engel, U., Lewis, A.L., Armes, S.P., and Tanaka, M. (2011). Quantitative Evaluation of Mechanosensing of Cells on Dynamically Tunable Hydrogels. Journal of the American Chemical Society 133, 1367-1374. 10.1021/ja1060615. Hörning, M., Nakahata, M., Linke, P., Yamamoto, A., Veschgini, M., Kaufmann, S., Takashima, Y., Harada, A., and Tanaka, M. (2017). Dynamic Mechano-Regulation of Myoblast Cells on Supramolecular Hydrogels Cross-Linked by Reversible Host-Guest Interactions. Scientific Reports 7, 7660. 10.1038/s41598-017-07934-x. Hayashi, K., Matsuda, M., Mitake, N., Nakahata, M., Munding, N., Harada, A., Kaufmann, S., Takashima, Y., and Tanaka, M. (2022). One-Step Synthesis of Gelatin-Conjugated Supramolecular Hydrogels for Dynamic Regulation of Adhesion Contact and Morphology of Myoblasts. ACS Applied Polymer Materials 4, 2595-2603. 10.1021/acsapm.1c01902. Hippler, M., Weißenbruch, K., Richler, K., Lemma, E.D., Nakahata, M., Richter, B., Barner-Kowollik, C., Takashima, Y., Harada, A., Blasco, E., et al. (2020). Mechanical stimulation of single cells by reversible host-guest interactions in 3D microscaffolds. Science Advances 6, eabc2648. 10.1126/sciadv.abc2648. 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