Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction

Area of Science:

• Biomaterials Science
• Cell Biology
• Nanotechnology

Background:

• Controlling molecular self-assembly within living cells for biological function actuation is complex.
• Existing methods lack precise spatiotemporal control and effective characterization tools for intracellular environments.

Purpose of the Study:

• To develop an organelle-localized self-assembly strategy for controlling cellular fate.
• To investigate the potential of peptide amphiphiles for targeted intracellular therapeutic applications.

Main Methods:

• Synthesized a phenylalanine dipeptide (FF) with a mitochondria-targeting moiety (triphenyl phosphonium), creating Mito-FF.
• Utilized confocal laser scanning microscopy and transmission electron microscopy to monitor nanostructure formation.
• Assessed the impact of Mito-FF self-assembly on mitochondrial function and cellular apoptosis.

Main Results:

• Mito-FF preferentially accumulated in mitochondria, reaching critical aggregation concentration to form fibrous nanostructures.
• The self-assembled Mito-FF fibrils disrupted mitochondrial membranes, inducing dysfunction.
• Mitochondrial dysfunction triggered apoptosis, demonstrating controlled cellular fate alteration.

Conclusions:

• Organelle-specific supramolecular systems, like Mito-FF in mitochondria, offer a novel approach for controlling cellular fate.
• This strategy opens new avenues for therapeutic interventions and detailed studies of cellular functions.