High-Throughput Screening of pH-Dependent β-sheet Self-Assembling Peptide.

Area of Science:

• Biomaterials Science
• Peptide Chemistry
• Nanotechnology

Background:

• pH-dependent peptide biomaterials are promising for cell delivery and tissue engineering.
• Identifying self-assembling peptide sequences with specific secondary structures responsive to pH changes is challenging.

Purpose of the Study:

• To develop a high-throughput screening method for identifying pH-dependent self-assembling β-sheet peptides.
• To discover peptide sequences that self-assemble at neutral pH and disassemble at acidic pH for biomaterial applications.

Main Methods:

• Utilized a one-bead one-compound (OBOC) combinatorial library approach.
• Employed thioflavin T (ThT) as a fluorescent probe to detect peptide self-assembly at pH 7.5.
• Selected peptides that lost fluorescence (disassembled) upon transfer to pH 6.5.

Main Results:

• Identified three heptapeptides capable of self-assembly into nanofibers or nanoparticles at pH 7.5 and disassembly at pH 6.5.
• Observed rapid acid response and morphology transformation in peptide P1 (LVEFRHY).
• Postulated that histidine charge and phenylalanine motif influence pH-responsive β-sheet nanofiber formation.

Conclusions:

• The OBOC library method is efficient for discovering pH-dependent β-sheet self-assembling peptides.
• This screening approach aids in understanding the structural design principles for responsive nanomaterials.
• The identified peptides show potential for advanced applications in regenerative medicine and drug delivery.