Self-assembly of model amphiphilic peptides in non-aqueous solvents: changing driving forces, same structure?

Within the homologous series of amphiphilic peptides AnK, both A8K and A10K self-assemble in water to form twisted-ribbon fibrils with lengths around 100 nm [1]. The structure of the fibrils can be described in terms of twisted -sheets extending in the direction of the fibril, laminated to give a constant cross section of 4 nm by 8 nm. A simple model considering a free energy penalty due to stretching of hydrogen bonds within -sheets arising from the twist of the ribbons [2], and the interfacial free energy of the hydrophobic -sheets which would favor their lamination, was able to reasonably predict the finite width of the twisted ribbons [3]. In this study, we characterize the self-assembly behavior of these peptides in non-aqueous solutions as a way to probe the role of the hydrophobic interaction in fibril stabilization. Both peptides in methanol and N,N-dimethylformamide were found to form fibrillar aggregates with the same -sheet structure and similar cross-section sizes as in water. However, the gel-like texture, the slow relaxation in DLS experiments, and a correlation peak in the SAXS pattern highlighted enhanced inter-fibrils interaction in the non-aqueous solvents, in the same concentration range (Figure 1). This could be ascribed to a higher effective volume of the aggregates due to enhanced fibril growth and length, as suggested by LS and cryo-TEM analysis. These effects can be discussed considering how the solvent properties affect the different energetic contributions (hydrophobic, electrostatic, H-bonding) to fibril formation. In the analyzed case the decreased H-bonding propensity of the non-aqueous solvents made the H-bond formation along the fibril a key driving force to the peptide assembly, whereas it represents a non-relevant contribution in water [4]. References [1] C. C. Cenker, S. Bucak, U. Olsson, Langmuir, 30 (33) 2014, 10072–10079. [2] A. Aggeli et al., Proc. Natl. Acad. Sci., 98 (21) 2001, 11857–11862. [3] A. Rüter, S. Kuczera, D. J. Pochan, U. Olsson, Langmuir 2019, acs.langmuir.8b03886 (just accepted) [4] I. M. Klotz, J. S. Franzen, J. Am. Chem. Soc., 84 (18) 1962, 3461–3466.