Liquid-liquid phase separation (LLPS) is a universal phenomenon that plays a key role in many biological processes. Although LLPS is well known for (bio)macromolecular systems, we have recently demonstrated that supramolecular polymer systems can also undergo LLPS via an entropy-driven pathway. This opens new avenues for engineering biomaterials with tailored properties and functionalities by modulating the pathways of supramolecular polymerization. On the other hand, we have also shown that the energy landscape of supramolecular polymerization can be manipulated via light-matter strong coupling, without any chemical or real photon as input. Intrigued by these recent observations, we employed light-matter strong coupling to control LLPS driven by non-covalent high aspect ratio supramolecular polymers. Studies using confocal microscopy, atomic force microscopy (AFM), and dynamic light scattering (DLS) revealed that the energy landscape of the supramolecular polymerization of ureido-pyrimidinone glycine (UPy-Gly) fibrils is modified when the vibrational bands of the molecular components are strongly coupled to the optical mode of the Fabry-Perot cavity, leading to the deceleration of LLPS kinetics. Moreover, strong coupling persists in retarding LLPS kinetics even in the presence of a macromolecular crowder, however the effect is mitigated by the crowder. This offers insights into the fundamentals of strong coupling. Additionally, these results reinforce the finding that a critical fibril length is required for LLPS initiation. This study underscores the potential of light-matter strong coupling in tuning the behavior and assembly of supramolecular systems.
