Peptide-induced membrane elastic deformations decelerate gramicidin dimer-monomer equilibration

Area of Science:

• Biophysics
• Membrane Biophysics
• Ion Channel Physics

Background:

• Gramicidin A (gA) forms ion channels in lipid bilayers via monomer dimerization.
• This process establishes a monomer-dimer equilibrium influencing membrane conductance.
• Perturbing this equilibrium leads to relaxation dynamics studied via electric current.

Purpose of the Study:

• Investigate the effect of N-terminal modifications on gA's dimerization kinetics.
• Determine how these modifications alter current relaxation times in response to conductance changes.
• Develop a theoretical model to explain observed deviations from classical gA behavior.

Main Methods:

• Synthesized gA analogs with N-terminal glycine or tyrosine substitutions.
• Measured macroscopic currents and relaxation kinetics across planar bilayer lipid membranes (BLMs).
• Developed a theoretical model incorporating lateral monomer-dimer interactions via membrane elastic deformations.

Main Results:

• gA analogs exhibited increased relaxation time with elevated membrane conductance, contradicting previous findings.
• The dimerization constant was found to decrease for these analogs.
• The theoretical model accurately predicted the reverse dependence of relaxation time on conductance.

Conclusions:

• Classical kinetic models for gA dimerization are insufficient for modified analogs.
• Lateral interactions mediated by membrane elastic deformations are crucial for understanding gA analog behavior.
• Peptide-membrane interactions and potential impurities significantly modulate ion channel equilibration.