Spontaneous membrane-translocating peptide adsorption at silica surfaces: a molecular dynamics study

Area of Science:

• Biophysics
• Materials Science
• Nanotechnology

Background:

• Spontaneous membrane-translocating peptides (SMTPs) possess the ability to directly penetrate cell membranes.
• Understanding peptide-surface interactions is key for developing novel biomaterials and drug delivery systems.

Purpose of the Study:

• To investigate the adsorption behavior of SMTPs and their engineered variants on model silica surfaces.
• To assess the potential of SMTPs for constructing advanced drug delivery systems.
• To elucidate the driving forces and conformational changes during peptide adsorption.

Main Methods:

• Fully atomistic molecular dynamics simulations were employed.
• Simulations mimicked electric fields above siloxide-rich charged silica surfaces.
• The effects of salt concentration and surface hydroxylation were systematically studied.

Main Results:

• Electrostatic interactions were identified as the primary driving force for SMTP adsorption.
• Increased salt concentration reduced adsorption rate but did not prevent adsorption or cause desorption, indicating hydrophobic contributions.
• Engineered peptide extensions enhanced adsorption without altering the final conformation.
• Peptide adsorption resulted in a flattened conformation, with key arginine residues anchoring to the surface.

Conclusions:

• SMTP adsorption to silica is governed by a combination of electrostatic and hydrophobic forces.
• The observed flattened adsorption conformation, with buried arginine residues, has significant implications for membrane translocation efficiency.
• These findings provide critical insights for the rational design of peptide-based drug delivery vehicles.