Communication Macromolecular Rapid Communications 426 DOI: 10.1002/marc.201100689 1. Introduction Self-assembly of molecular building block into ordered nanostructures not only plays a vital role in various biolog- ical phenomena but also provides an important guidance for design and fabrication of novel nanomaterials. In par- ticular, peptide-based self-assemblies have drawn much attention because of their unique properties including well biocompatibility, chemical versatility, and biological recog- nition abilities. [1–4] To date, self-assembled peptide-based materials have become a class of very important biocompat- ible materials that have found various applications in tissue engineering, [5–7] drug delivery, [8–10] wound healing, [11,12] and inhibitor screening. [13,14] The self-assembly of peptide can be generally divided into two categories: spontaneous self-assembly and induced self-assembly. The latter one has attracted significant attention because the properties of the self-assembled peptide can be adjusted in response to the local environmental stimuli. In the past few dec- ades, various strategies such as heating–cooling cycle, [15] light irradiation, [16–18] pH, [19–22] and enzymatic triggera- tion [23–26] have been reported to regulate the self-assembly of peptides and their derivatives. Recently, disulfide bond reduction with a similar principle as enzymatic triggera- tion has been also developed. [27–29] Of the above strategies, enzymatic triggeration is more beneficial than the other ones for biomedical applications because of the mild self- assembling conditions and low level of damage to body tissues. It is known that enzymes widely involve various biological reactions in organism. Therefore, developing of a self-assembling system in response to enzyme triggered biological reactions is of great importance to construct new materials for biomedical applications. In this study, we reported a new type of peptide-based self-assembly in response to biological glucose metabolism. Glucose is well recognized as the energy source of biological metabolism. The glycolysis of glucose is reported to be a complicated metabolic pathway that converts glucose into pyruvic acid with the aid of various kinds of enzymes including kinase, aldolase, isomerase, and enolase. [30] Here, we con- structed a biological glucose metabolism system by using glucose oxidase (GOx) and investigated its influence on A glucose oxidase (GOx)-mediated glucose metabolism was in vitro mimicked and employed to regulate the self-assembly of peptide-based building blocks. In this new stimuli-responsive self-assembly system, two peptide-based building blocks, respectively, having aspartic acid (gelator 1) and lysine (gelator 2) residues were designed and prepared. When adding glucose and GOx to the aqueous solution of gelator 1 or the self-assembled fibrillar hydrogel of gelator 2 to construct glucose metabolism system, the metabolic product (gluconic acid) can trigger the protonation of the pep- tide molecules and induce the phase transitions of gelators 1 (sol-gel) and 2 (gel-sol). Because this glucose metabolism reg- ulated peptide self-assembly is built on the oxidation of glu- cose, it can be used as a simple visual biosensor for glucose detection. Biological Glucose Metabolism Regulated Peptide Self-Assembly as a Simple Visual Biosensor for Glucose Detection Xiao-Ding Xu, Bing-Bing Lin, Jun Feng, Ya Wang, Si-Xue Cheng, Xian-Zheng Zhang*, Ren-Xi Zhuo X.-D. Xu, B.-B. Lin, J. Feng, Y. Wang, S.-X. Cheng, X.-Z. Zhang, R.-X. Zhuo Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China Fax: +86-27-68755993 E-mail: xz-zhang@whu.edu.cn Macromol. Rapid Commun. 2012, 33, 426−431 © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com