Self-assembly pathways and polymorphism in peptide-based nanostructures

Abstract

Dipeptide derivative molecules can self-assemble into space-filling nanofiber networks at low volume fractions (<1%), allowing the formation of molecular gels with tunable mechanical properties. The self-assembly of dipeptide-based molecules is reminiscent of pathological amyloid fibril formation by naturally occurring polypeptides. Fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) is the most widely studied such molecule, but the thermodynamic and kinetic phenomena giving rise to Fmoc-FF gel formation remain poorly understood. We have previously presented evidence that the gelation process is a first order phase transition characterized by low energy barriers to nucleation, short induction times, and rapid quasi-one-dimensional crystal growth, stemming from solvent-solute interactions and highly specific molecular packing. Here, we discuss the phase behavior of Fmoc-FF in different solvents. We find that Fmoc-FF gel formation can be induced in apolar solvents, in addition to previously established pathways in aqueous systems. We further show that in certain solvent systems anisotropic crystals (nanofibers) are an initial metastable state, after which macroscopic crystal aggregates with no preferred axis of growth are formed. The molecular conformation is sensitive to solvent composition during assembly, indicating that Fmoc-FF may be a simple model system to study complex thermodynamic and kinetic phenomena involved in peptide self-assembly.

Topochemical synthesis of different polymorphs of polymers as a paradigm for tuning properties of polymers

“…Gels being a kinetically trapped metastable state, they can slowly transform to thermodynamically stable crystals [36][37][38][39] , often to polymorphs that are inconceivable from the normal solutionstate crystallization 36,[40][41][42][43][44] . Remarkably, the organogels of DP (≥4 wt%) slowly transformed to crystals over a period of time when left undisturbed.…”

Multicomponent peptide assemblies

“…While the same noncovalent interactions govern the formation of single component self-assembled peptide nanostructures and multicomponent coassembled nanostructures, 99–102 the kinetic and thermodynamic parameters that influence these processes are of special interest in the controlled coassembly of multicomponent materials. 102,103 Environmental factors such as temperature, 104,105 pH, 104–106 salt effects, 107–109 and solvent interactions 110–115 have been shown to influence the kinetics and thermodynamics peptide self-assembly in ways that dictate the ultimate supramolecular materials that are formed. When considering coassembly of multiple peptides, the kinetics and thermodynamics of both self-assembly and coassembly of the various components must be accounted for in order to selectively form the desired multicomponent materials.…”

Annealing multicomponent supramolecular gels

“…26,27 We use a solvent-triggered approach where the gelator is initially dissolved in a water-miscible solvent such as DMSO, followed by the addition of water. 9,[28][29][30][31][32] This drives a phase separation that results in spherulitic domains of fibers that entangle to form a self-supporting gel. 30,33,34 The gels formed by this method are kinetically trapped.…”