TEM showed that the self-assembled morphologies strongly depend on the pH conditions; that is, the self-assembly of566at pH 6. 1 gives fibers, but at pH 9. 2 gives sheets. prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping address fundamental questions about the mechanisms or the consequences of the self-assembly of molecules, including low molecular weight ones. Finally, we provide a perspective on supramolecular hydrogelators. We hope that this review will serve as an updated introduction and reference for researchers who are interested in exploring supramolecular hydrogelators as molecular biomaterials for addressing the societal needs at various frontiers. == 1 . Introduction == == 1 . 1 . Hydrogelators and Hydrogels == Molecular self-assembly is a ubiquitous process in nature, and is also believed to play an essential role in the emergence, maintenance, and advancement of life. 13While the primary focus of the research on molecular self-assembly centers on the biomacromolecules (proteins, nucleic acids, and polysaccharides) or their mimics, the self-assembly of small molecules in water (or an organic solvent) also has profound implications from fundamental science to practical applications. Because one usual consequence of the self-assembly of the small molecules is the formation of a gel (or gelation), a subset of these small molecules is called gelators. Depending on the solvents in which they form gels, these small molecules are further classified as hydrogelators4(using water as the liquid phase) and organogelators5(using an organic solvent as the liquid phase). More precisely, hydrogelators (i. e., the molecules) self-assemble in water to form three-dimensional supramolecular networks that encapsulate a large amount of KN-92 phosphate water to afford an aqueous mixture. The aqueous mixture is a supramolecular hydrogel because it exhibits viscoelastic behavior of a gel (e. g., unable to flow without shear force). Unlike the conventional polymeric hydrogels that are mainly based on covalently cross-linked networks of polymers (i. e., gellant), the networks in supramolecular hydrogels are formed due to noncovalent interactions between the hydrogelators (Figure1A). 6Considering that water is the unique solvent to maintain life forms on earth, it is important and necessary to distinguish water from organic solvents. Because supramolecular hydrogels are a type of relatively simple heterogeneous system that consists of a large amount of water, it is not surprising that the applications of hydrogels and hydrogelators in life science have advanced most significantly. Thus, in this review we Itga6 mainly focus on the works that KN-92 phosphate study the properties and explore the applications of supramolecular hydrogels and hydrogelators in biomedical science. Because of the rapid advancement of the field, it is unavoidable that some works are inadvertently absent from this review. Here we offer our sincere apology in advance and hope readers will let us know those deserving works so we can include them in future reviews. == Figure 1 . == (A) Illustration of the process for creating polymeric hydrogels via cross-linking (left), or formation of supramolecular hydrogels via a KN-92 phosphate chemical or physical perturbation initiated self-assembly (right). Adapted with permission from ref (6). Copyright 2006 Wiley-VCH Verlag GmbH & Co. KGaA. (B) Molecular structures of1and2. (C) Molecular structure of Nap-FF (3). (D) Optical image and negatively stained TEM image of the hydrogel of3. Adapted from ref (14). Copyright 2011 American Chemical Society. == 1 . 2 . History and Serendipity == According to the report by Hoffman in 1921, the first small molecule hydrogelator was dibenzoyl-l-cystine (1) (Figure1), which was able to form a gel of 0. 1% concentration [that] was rigid enough to hold its shape for a minute or more when the beaker containing the gel was inverted. 7Interestingly, the same hydrogel was reported by Brenzinger almost 20 years earlier. 8However, not until a century later did Menger et al. use modern physical methods in chemistry (e. g., X-ray crystallography, light and electron microscopy, rheology, and calorimetry) to examine the hydrogel of1again and provide invaluable molecular details that reveal many fundamental design principles for creating effective hydrogelators made of small molecules. Impressively, among the 14 aroyl-l-cystine derivatives studied by Menger in the seminal work KN-92 phosphate in 2000, 9the best hydrogelator (2) is able to self-assemble and to rigidify aqueous solutions at 0. 25 mM, ca. 0. 01 wt %, in less than 30 s, which probably still holds the record in terms of the lowest concentration of hydrogelators and the fastest rate for gelation. 10One of the most revealing design principles in the study of1is that aromatic moieties are highly effective for enhancing intermolecular interactions in water. This principle is largely responsible for the successful use of aromaticaromatic interactions to design hydrogelators of small peptides. 11, 12Not surprisingly, nature has already used aromaticaromatic interactions to evolve proteins. 13These facts imply.