The Peculiar Response of DNA Hydrogel Fibers to a Salt and pH Stimulus Sun Hee Lee, Chang Kee Lee, Su Ryon Shin, Sun I. Kim, Insuk So, Seon Jeong Kim * Introduction Recently, DNA hydrogels have been fabricated as remark- able biocompatible, biodegradable, and inexpensive mate- rials [1] that can be applied in a wide range of bioengineer- ing applications, such as drug delivery systems and in tissue engineering. [1,2] DNA hydrogels are also expected to be used in bio-artificial muscles, [3] because DNA responds to stimulus by salt and pH. [4,5] This response by DNA arises from the electrostatic repulsion of the phosphate groups of DNA and from the hydrophobic interaction of the base pairs of the flexible DNA backbone. A double DNA strand has been shown to be sensitive to conformational changes attributed to electrostatic interactions and steric and hydration effects between the DNA and cations, [6] as such cations are bound to the phosphate groups of DNA. In this conformational change, the long DNA strands undergo a distortion to form a globular shape from the usual linear shape. Thus, the flexible backbone of a DNA hydrogel assures an active volume change though this active conformational change. DNA strands can also show the conformational changes from changes in pH, because a DNA backbone undergoes protonation in acidic media (pH < 2) due to the pKa value of the phosphate groups (pKa ¼ 1.2). [7] The DNA hydrogel fibers we developed were shaped into fibers through a randomly intertwined and entangled network of individual DNA strands, where any chemical modification to form crosslinking networks was excluded. [8] This means that the response of these DNA hydrogel fibers to pH and salt reflected the conformational changes of a single DNA strand. Namely, the response of the DNA hydrogel fibers could be understood by the well known conformational changes of DNA strands in response to salt and changes in pH. However, we have not found any studies in the literature on the Communication S. H. Lee, C. K. Lee, S. R. Shin, S. I. Kim, I. So, S. J. Kim Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Korea Fax: þ82-2-2291-2320; E-mail: sjk@hanyang.ac.kr I. So Department of Physiology, Seoul National University, Seoul 110-744, Korea DNA hydrogels which are composed of an entangled network without a crosslinker are synthesized and examined in regards to their sensitivity to salt and pH changes. The DNA hydrogel fibers only exhibited a marked response – that is a fast and large change in length – under biological conditions ([Na þ ] ¼ 0.15 M at pH ¼ 7) and are therefore suitable materials for bio-inspired devices. 430 Macromol. Rapid Commun. 2009, 30, 430–434 ß 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/marc.200800677