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Please use this identifier to cite or link to this item: http://hdl.handle.net/10119/13702

Title: Toward a Molecular Understanding of the Mechanism of Cryopreservation by Polyampholytes: Cell Membrane Interactions and Hydrophobicity
Authors: Rajan, Robin
Hayashi, Fumiaki
Nagashima, Toshio
Matsumura, Kazuaki
Keywords: cryoprotective agent
hydrophobicity
membrane
polyampholyte
polymer
zwitterionic
Issue Date: 2016-04-14
Publisher: American Chemical Society
Magazine name: Biomacromolecules
Volume: 17
Number: 5
Start page: 1882
End page: 1893
DOI: 10.1021/acs.biomac.6b00343
Abstract: Cryopreservation enables long-term preservation of cells at ultra-low temperatures. Current cryoprotective agents (CPAs) have several limitations, making it imperative to develop CPAs with advanced properties. Previously, we developed a novel synthetic polyampholyte based CPA, copolymer of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and methacrylic acid(MAA), (poly-(MAA-DMAEMA)) which showed excellent efficiency and biocompatibility. Introduction of hydrophobicity increased its efficiency significantly. Herein, we investigated the activity of other polyampholytes. We prepared two zwitterionic polymers, poly-sulfobetaine (SPB) and poly-carboxymethyl betaine (CMB) and compared its efficiency with poly-(MAA-DMAEMA). Poly-SPB showed only intermediate property and poly-CMB showed no cryoprotective property. These data suggested that the polymer structure strongly influences cryoprotection, providing an impetus to elucidate the molecular mechanism of cryopreservation. We investigated the mechanism by studying the interaction of polymers with cell membrane, which allowed us to identify the interactions responsible for imparting different properties. Results unambiguously demonstrated that polyampholytes cryopreserve cells by strongly interacting with cell membrane, with hydrophobicity increasing the affinity for membrane interaction, which enable it to protect the membrane from various freezing induced damages. Additionally cryoprotective polymers, especially their hydrophobic derivatives, inhibit the recrystallization of ice, thus averting cell death. Hence, our results provide an important insight into the complex mechanism of cryopreservation, which might facilitate the rational design of polymeric CPAs with improved efficiency.
Rights: Robin Rajan, Fumiaki Hayashi, Toshio Nagashima, and Kazuaki Matsumura, Biomacromolecules, 2016, 17(5), pp.1882-1893. This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Biomacromolecules, copyright (c) American Chemical Society after peer review. To access the final edited and published work, see http://dx.doi.org/10.1021/acs.biomac.6b00343
URI: http://hdl.handle.net/10119/13702
Material Type: author
Appears in Collections:c10-1. 雑誌掲載論文 (Journal Articles)

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