Aging-Dependent Morphological Crystallinity Determines Membrane Activity of l-Phenylalanine Self-Assembles

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Amyloid polymorphism is crucial for neurodegenerative diseases.
• The self-assembly and polymorphism of l-phenylalanine (l-Phe), a fundamental amino acid, are largely unexplored.
• Understanding l-Phe's structural variations is key to its biological and therapeutic implications.

Purpose of the Study:

• To provide the first evidence of l-phenylalanine (l-Phe) polymorphism.
• To investigate the conversion of l-Phe self-assembly structures with time and temperature.
• To analyze the distinct membrane interaction capabilities of different l-Phe polymorphs.

Main Methods:

• Investigated l-phenylalanine (l-Phe) self-assembly under varying time and temperature conditions.
• Characterized the structural morphologies of l-Phe aggregates using techniques like microscopy and spectroscopy.
• Assessed the interaction of l-Phe polymorphs with model cell membranes.

Main Results:

• Demonstrated the existence of l-Phe polymorphism, with metastable helical fibrils converting to stable rodlike crystals.
• Observed that only the fibrillar l-Phe polymorph significantly modulates model membranes.
• Found that l-Phe molecules favor multilayered rodlike arrangements, reducing membrane binding affinity due to altered N-terminal charge.

Conclusions:

• l-Phenylalanine (l-Phe) exhibits polymorphism, influencing its self-assembly and properties.
• The fibrillar l-Phe polymorph's unique membrane interaction offers potential therapeutic strategies.
• This research provides a novel perspective on l-Phe self-assembly and its implications for phenylketonuria treatment.