Selective Self-Assembly of 5-Fluorouracil through Nonlinear Solvent Response Modulates Membrane Dynamics

Area of Science:

• Biophysics
• Materials Science
• Neurodegenerative Disorders

Background:

• Self-assembly of metabolite fibrils is crucial for understanding neurodegenerative diseases.
• Interactions between fibrils and cell membranes are key to developing treatments.

Purpose of the Study:

• To achieve controllable self-assembly of 5-fluorouracil (5-FU) fibrils.
• To investigate the impact of these fibrils on live-cell membranes.
• To understand the role of solvent in self-assembly.

Main Methods:

• Utilizing dimethyl sulfoxide (DMSO)-water mixtures to induce selective self-assembly.
• Employing excited-state dynamics to correlate water availability with self-assembly.
• Analyzing the modulation of live cell membrane fluidity and lipid distribution.

Main Results:

• Selective self-assembly of 5-FU fibrils was achieved by controlling DMSO-water mixtures.
• 5-FU fibrils were shown to modulate live cell membrane fluidity and lipid distribution.
• Fibril addition disordered hydrogen-bonded water molecules, altering interfacial water structure and dynamics.

Conclusions:

• Solvent properties, specifically water availability, govern the specific self-assembly of metabolites like 5-FU.
• These findings provide insights into early disease stages and multidrug resistance mechanisms.
• The study highlights the potential of controlled fibril self-assembly for therapeutic strategies.