Phase Transition and Crystallization Kinetics of a Supramolecular System in a Microfluidic Platform

Supramolecular self-assembly is a key process in natural systems, allowing for the formation of structures across all length scales with a wide range of functionalities. Notable progress has been made in the bottom-up design and generation of natural and artificial peptides, which through self-assembly provide diverse nano- and microscale architectures for a variety of applications. These systems possess advantageous properties including facile synthesis and biocompatibility. However, their self-assembly into distinct structural species, particularly in relation to the underlying kinetic and dynamic mechanisms involved, remain challenging to determine. Here, we study the self-assembly of Fmoc-pentafluoro-phenylalanine (Fmoc-F5-Phe), a modified amino acid, shedding light on those key processes. We show that Fmoc-F5-Phe forms diverse architectures, including fibrils, ribbons, and crystals, modulated by the solution conditions in which self-assembly takes place. We further elucidate the specific molecular interactions, which play a role in crystal structure formation using powder X-ray diffraction (PXRD). Finally, by probing the self-assembly of Fmoc-F5-Phe using a microfluidic platform, we reveal the formation of transient spherical assemblies, followed by a gel composed of fibrils and finally crystals and monitor these structural transitions in real time. Furthermore, we show that the kinetic behavior of the crystallization process adheres to the Johnson–Mehl–Avrami–Kolmogorov (JMAK) model of phase transformation rate. This work provides an experimental and theoretical framework into the kinetics and dynamics of the supramolecular self-assembly processes of amino-acid-based building blocks, leading to the design of tailor-made materials for biomedical and material science applications.