Fibrillar Structure of Methylcellulose Hydrogels Joseph R. Lott, † John W. McAllister, † Sara A. Arvidson, † Frank S. Bates,* ,‡ and Timothy P. Lodge* ,†,‡ † Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States ‡ Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota 55455, United States * S Supporting Information ABSTRACT: It is well established that aqueous solutions of methylcellulose (MC) can form hydrogels on heating, with the rheological gel point closely correlated to the appearance of optical turbidity. However, the detailed gelation mechanism and the resulting gel structure remain poorly understood. Herein the fibrillar structure of aqueous MC gels was precisely quantified with a powerful combination of (real space) cryogenic transmission electron microscopy (cryo-TEM) and (reciprocal space) small-angle neutron scattering (SANS) techniques. The cryo-TEM images reveal that MC chains with a molecular weight of 300 000 g/mol associate into fibrils upon heating, with a remarkably uniform diameter of 15 ± 2 nm over a range of concentrations. Vitrified gels also exhibit heterogeneity in the fibril density on the length scale of hundreds of nanometers, consistent with the observed optical turbidity of MC hydrogels. The SANS curves of gels exhibit no characteristic peaks or plateaus over a broad range of wavevector, q, from 0.001−0.2 Å −1 . The major feature is a change in slope from I ∼ q −1.7 in the intermediate q range (0.001 − 0.01 Å −1 ) to I ∼ q −4 above q ≈ 0.015 Å −1 . The fibrillar nature of the gel structure was confirmed by fitting the SANS data consistently with a model based on the form factor for flexible cylinders with a polydisperse radius. This model was found to capture the scattering features quantitatively for MC gels varying in concentration from 0.09−1.3 wt %. In agreement with the microscopy results, the flexible cylinder model indicated fibril diameters of 14 ± 1 nm for samples at elevated temperatures. This combination of complementary experimental techniques provides a comprehensive nanoscale depiction of fibrillar morphology for MC gels, which correlates very well with macro-scale rheological behavior and optical turbidity previously observed for such systems. C ellulose ethers are a class of polymers that have received substantial commercial and academic interest. Methyl- cellulose (MC), a semiflexible linear-chain polysaccharide, has the most straightforward chemical composition among cellulose derivatives with a partial replacement of hydroxyl groups with methoxy moieties. The average number of methoxy groups per anhydroglucose unit is quantified by the degree of substitution (DS), which ranges from zero for unmodified cellulose to a maximum of three, corresponding to a fully substituted chain. The balance between hydrophilic hydroxyl and hydrophobic methoxy groups dictates the aqueous solubility of the polymer. Typically, a DS of ∼1.6 − 2.1 confers low temperature water solubility to the polymer, while phase separation and gelation occur at elevated temperatures. Although this behavior of aqueous MC solutions has been studied for decades, there is no consensus on the mechanism involved in the sol−gel transition. For example, the phase separation previously has been interpreted as a spinodal process, 1−3 whereas we have recently argued in favor of a nucleation and growth mechanism. 4 In particular, the relation- ship between the lower critical solution temperature (LCST) and the gelation process is a matter of much debate. It is has been suggested that MC gelation could result from “pinned” liquid−liquid phase separation, in which the polymer-rich and polymer-deficient phases become kinetically trapped. 3,5,6 Alternatively, some groups have found that phase separation and gelation occur simultaneously. 4,7,8 The specific molecular interactions that drive these processes are also unclear. In the low temperature pregel state, bundles of residual native cellulose crystals, 8,9 intermolecular hydrogen bonding between unmodified hydroxyl groups along the chains, 10,11 and liquid crystal phases 12 have all been claimed to play an important role. In the gel state, network formation has variously been postulated to result from micellar interactions, 13−15 crystallites consisting of trimethylated glucose rings, 16 hydrophobic interactions, 5,7,10,11,17 and entangled physical cross-links that phase separate from the solvent. 18 Recently, we reported a study aimed at clarifying the relationship between phase separation and gelation for aqueous MC solutions. 4 The rheological behavior of three different samples with similar DS and with sufficient concentration (c ≥ 10c* where c* is the overlap concentration) was found to follow the Winter-Chambon criterion for gelation, using a very slow heating rate (∼2 °C/h). 19 This provided an unambiguous definition of the gelation temperature (T gel ), which was independent of measurement frequency. Using the same thermal treatment as in the rheological experiments, cloud points of MC solutions were measured to determine the Received: May 14, 2013 Revised: July 5, 2013 Published: July 26, 2013 Communication pubs.acs.org/Biomac © 2013 American Chemical Society 2484 dx.doi.org/10.1021/bm400694r | Biomacromolecules 2013, 14, 2484−2488