Peptides@mica: from affinity to adhesion mechanism.

Area of Science:

• Surface chemistry
• Biomaterials science
• Computational biophysics

Background:

• Peptide adsorption on inorganic surfaces is crucial for biochips and implantation medicine.
• Understanding molecular interactions is key for designing effective biomaterials.
• RTHRK is a positively charged pentapeptide known to bind oxidized silicon.

Purpose of the Study:

• To investigate the adsorption of the pentapeptide RTHRK and its analogues on negatively charged mica surfaces.
• To develop and validate an efficient method for quantifying peptide binding affinity and adhesion.
• To elucidate the atomistic mechanisms governing peptide-surface interactions using complementary experimental and computational approaches.

Main Methods:

• Atomic Force Microscopy (AFM) to measure surface coverage and adhesion free energy.
• Knowledge-based fitting to AFM image autocorrelation for bias correction.
• Large-scale Molecular Dynamics (MD) simulations to explore binding affinities and mechanisms.
• Thermodynamic analysis linking surface coverage to adhesion energy.

Main Results:

• Homogeneous monolayer formation of RTHRK and analogues on mica at low concentrations.
• An efficient method combining AFM and thermodynamics for binding affinity quantification.
• MD simulations and AFM data revealed that salt bridges and hydrogen bonds dictate binding affinity.
• Differences in hydrogen bonding, not just charge, cause significant variations in binding strength.

Conclusions:

• Peptide adsorption is governed by specific molecular interactions like salt bridges and hydrogen bonds.
• The developed AFM-based method offers an efficient way to study peptide-surface interactions.
• Combining AFM and MD simulations provides a powerful approach for understanding peptide adsorption at the atomistic level.
• This research advances the design of peptide-based biomaterials for various applications.