Speakers

​​The stabilization of biological systems against environmental stresses is a critical challenge in biotechnology, regenerative medicine, and biopharmaceutical applications. Functional polymers have emerged as promising materials for protecting living cells and biomacromolecules by regulating water structure, ion distribution, and molecular interactions. In this study, we present two classes of bioinspired polymers developed for cellular cryopreservation and protein stabilization.
First, we describe polyampholyte-based cryoprotectants derived from carboxylated poly(L-lysine) (COOH-PLL)[1]. Conventional cryopreservation relies heavily on dimethyl sulfoxide (DMSO), which often induces cytotoxicity and limits clinical applicability. In contrast, COOH-PLL exhibits excellent cryoprotective performance with reduced toxicity. The polymer significantly improves post-thaw viability in various mammalian cells and has been successfully applied to the preservation of stem cells, embryos, and three-dimensional cellular constructs. Physicochemical analyses indicate that the cryoprotective effect originates from the regulation of ice formation and the preservation of intracellular osmotic balance during freezing and thawing processes[2]. The ampholytic structure provides a unique hydration environment that suppresses freezing-induced cellular damage.
Second, we introduce sulfobetaine-based zwitterionic polymers as protein stabilizers[3]. Protein therapeutics frequently suffer from aggregation and denaturation during storage, transportation, and thermal stress. Sulfobetaine polymers possess highly hydrated ionic moieties that strongly interact with surrounding water molecules while minimizing direct adsorption onto protein surfaces. These characteristics enable efficient suppression of protein aggregation and preservation of native protein structures under various stress conditions. Spectroscopic and biochemical analyses reveal that the polymers maintain protein activity by stabilizing hydration shells and preventing unfavorable intermolecular interactions.
Despite targeting different biological systems, both polymer classes share a common design principle: the utilization of zwitterionic interactions to control water and ion behavior at biological interfaces. The results demonstrate that rationally designed functional polymers can serve as versatile platforms for protecting cells and proteins, providing new opportunities for cryobiology, biopharmaceutical formulation, regenerative medicine, and advanced biomaterials. Future developments integrating molecular design, spectroscopy, and quantitative structure–function relationships will further expand the potential of polymer-based bio-protection technologies.​

​​​References
[1] Matsumura, K., et al., “Polyampholytes as low toxic efficient cryoprotective agents with antifreeze protein properties,” Biomaterials, 30 (2009): 4842-4849.
[2] Matsumura, K., et al., “Molecular mechanisms of cell cryopreservation with polyampholytes studied by solid-state NMR,” Commun. Mater., 2(2021) 15.
[3] Rajan, R., et al., “Molecular mechanism of protein aggregation inhibition with sulfobetaine polymers and their hydrophobic derivatives,” Cell Rep. Phys. Sci., 5 (2024): 102012.​