Drying Affects the Fiber Network in Low Molecular Weight Hydrogels Laura L. E. Mears, † Emily R. Draper, †,‡ Ana M. Castilla, † Hao Su, § Zhuola, ∥ Bart Dietrich, †,‡ Michael C. Nolan, †,‡ Gregory N. Smith, ⊥ James Doutch, # Sarah Rogers, # Riaz Akhtar, ∥ Honggang Cui, § and Dave J. Adams* ,†,‡ † Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, United Kingdom ‡ School of Chemistry, WESTChem, University of Glasgow, Glasgow, G12 8QQ, United Kingdom § Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, United States ∥ Department of Mechanical, Materials and Aerospace Engineering, School of Engineering, University of Liverpool, Liverpool L69 3GH, United Kingdom ⊥ Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, United Kingdom # STFC ISIS Neutron and Muon Source, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell Oxford, Didcot, OX11 0QX, United Kingdom * S Supporting Information ABSTRACT: Low molecular weight gels are formed by the self-assembly of a suitable small molecule gelator into a three-dimensional network of fibrous structures. The gel properties are determined by the fiber structures, the number and type of cross-links and the distribution of the fibers and cross-links in space. Probing these structures and cross-links is difficult. Many reports rely on microscopy of dried gels (xerogels), where the solvent is removed prior to imaging. The assumption is made that this has little effect on the structures, but it is not clear that this assumption is always (or ever) valid. Here, we use small angle neutron scattering (SANS) to probe low molecular weight hydrogels formed by the self-assembly of dipeptides. We compare scattering data for wet and dried gels, as well as following the drying process. We show that the assumption that drying does not affect the network is not always correct. ■ INTRODUCTION Low molecular weight gels (LMWG) are receiving a lot of attention. 1−9 Unlike covalently cross-linked polymer gels, LMWG are formed when small molecules self-assemble into one-dimensional structures such as fibrils, fibers, or tubes. At a sufficiently high concentration (the so-called minimum gelation concentration (mgc)), these structures entangle and branch to a sufficient degree that a sample spanning network is formed. This immobilizes the solvent, resulting in a gel. Typically, the mgc will be less than 1 wt%. Such gels are reversible, for example reverting to a solution on heating. 7 For peptide-based LMWG, the main driving forces of gel formation are noncovalent interactions. Changes in temperature or pH and the addition of salts can all lead to changes in the interactions between LMWG molecules that drive self-assembly into a kinetically trapped state. The kinetics and thermodynamics of dipeptide gelation, specifically focusing on diphenylalanine, has been reviewed recently, 10 although the thermodynamic aspects of gelation remain less well understood. Drying could lead to changes in the kinetically trapped structures to a thermody- namic energy minimum such as crystallization or the fibers could be maintained. There is significant interest in such gels for applications in cell culturing, 4,11 controlled release, 12 optoelectronics, 5 drug therapies, 13 and oil recovery. 14 For these applications, key properties include the absolute mechanical strengths, the recoverability after shear (for example, in drug delivery where the gel would be passed through a needle), 15 or the thermal reversibility. 16,17 All of these properties depend on the fiber network, which means that characterizing and understanding this network is absolutely vital. To characterize such gels, a range of methods have been used. Rheological methods inform as to the mechanical properties, but the network type has to then be inferred. 18,19 Techniques such as infrared spectroscopy or circular dichroism Special Issue: Organized Peptidic Nanostructures as Functional Materials Received: June 13, 2017 Revised: June 19, 2017 Published: June 20, 2017 Article pubs.acs.org/Biomac © XXXX American Chemical Society A DOI: 10.1021/acs.biomac.7b00823 Biomacromolecules XXXX, XXX, XXX−XXX This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.