Regular ArticleA shear-induced network of aligned wormlike micelles in a sugar-based molecular gel. From gelation to biocompatibility assays
Graphical abstract
Introduction
Low molecular weight (LMW) hydrogelators provide an alternative family of gelling agents compared with polymers, leading to soft materials with possible applications in the field of wet materials, switchable gels, controlled release or uptake, cell culture. LMW gelators belong to different structural families (peptides, cholesteryl, nucleobase or sugar amphiphiles, etc…) and the now quite large amount of work done on these self-assembling molecules has been well reported in several reviews [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]. We are more especially interested in sugar-derived molecular gelators (see the recent review on this family of gelators and the following references for the most recent works [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50]). Sugar gelators provide generally a neutral hydrophilic polar head, with a low sensitivity to temperature changes on the contrary to PEG amphiphiles. In the context of biological applications, carbohydrate derived hydrogels will interact differently with biomolecules or cells compared with PEG or peptide derived gelators, notably by mimicking to some extent the saccharidic components of the glycocalix, composed of glycoproteins and glycolipids [22].
From a practical point of view, simple, rapid and cheap syntheses are essential when considering sugar-based LMW hydrogelators applications. In former results, a family of hydrogelators based on a disaccharide head has been described. It has been shown that the presence of a triazole linker enhanced gelation, but the synthetic pathway consisted of six steps [23], [24], [25], [26]. Other amphiphilic molecules with close structures (namely, a sugar head, triazole linkers, and a fatty chain) have been described as well, including hydrogelators [27], [28], [29], organogelators [30] and micelles [31], [32], [33], all of them involving also protection-deprotection multistep synthesis and purification by chromatography. In this work, a new gelator inspired from these structures has been prepared with a simpler synthetic route with only three steps starting from lactobionic acid as the polar head (Scheme 1). Another important aspect in the field of LMW hydrogelators is to control in a precise manner the supramolecular structure sustaining the gel. In the case of very flexible molecules many conformations are possible. It can give rise to polymorphism. Polymorphism is the main cause for the lack of reproducible gelation [34], [35], [36], [37]. Accordingly, the importance of controlling the conditions of the self-assembly in order to reach a reproducible final state, with the related macroscopic properties, has been well pointed out in several papers. But it still remains underestimated, quite unexplored and not well controlled [38], [39], [40], [41], [42]. Compound 3 is a typical example of such a situation. Its gelation behaviour appeared more complex than expected and gave the opportunity to explore the effect of different pathways for the gel preparation. The self-assembled structures have been elucidated by electronic microscopy and Small Angle X-ray Scattering (SAXS). The rheology and thermal transitions of the gel have also been studied. Finally, the results related to the use of these gels for cell culture are briefly discussed.
Section snippets
Preparation of the gelator
An easy access to the sugar based gelator 3 is represented in Scheme 1. The gelator was obtained in three synthetic steps and was purified without chromatography. The fatty chain 1 was purified by recrystallization (yield 60%) while the product 2 was obtained nearly pure by extraction and was used without further purification in the next step. After the azide-alkyne “click chemistry” step, leading to the compound 3, the unreacted and sparingly soluble azide was discarded by centrifugation. The
Conclusions
This new sugar-based gelator, despite an easy synthetic access, displayed quite a complex gelation behaviour in pure water due to polymorphism. The presence of two amides bonds, but separated from each other by a rigid spacer (triazole), forces the molecule to bend and favours the polymorphism. This observation may help the design of gelators. Without shearing, the gelation was capricious. Starting from 2 wt% solutions and applying a strong shear enabled to get reproducible gelation. The
Acknowledgements
We acknowledge the following people for their technical assistance: TEM: I. Fourquaux, D. Goudounèche (CMEAB); V. Sartor, S. Gineste (IMRCP); NMR: P. Lavedan, M. Vedrenne (ICT). We acknowledge the European Union for funding (AFM, DSC) (FEDER 35477: “Nano-objets pour la biotechnologie”) and The French National Research Agency (ANR) for financial support (ANR Neuraxe). We thank the Integrated Screening Platform of Toulouse (PICT, IBiSA) for providing access to HPLC equipment. LB and EF kindly
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