Lateral dynamics of proteins with polybasic domain on anionic membranes: a dynamic Monte-Carlo study

Area of Science:

• Biophysics
• Computational Biology
• Cellular Biophysics

Background:

• Positively charged polybasic domains are crucial for recruiting signaling proteins to negatively charged cell membranes.
• The influence of electrostatic interactions on the lateral dynamics of these proteins remains less understood.

Purpose of the Study:

• To investigate the impact of electrostatic interactions on the lateral dynamics of adsorbed oligopeptides and anionic lipids.
• To simulate the behavior of peptides and lipids within a bilayer using a dynamic Monte-Carlo automaton.

Main Methods:

• Developed a dynamic Monte-Carlo automaton for simulating lateral diffusion.
• Modeled adsorption and dynamics of positively charged oligopeptides.
• Simulated dynamics of monovalent (phosphatidylserine) and polyvalent (PIP(2)) anionic lipids.

Main Results:

• Simulations confirmed lipid demixing, forming a peptide-associated lipid shell.
• Tetravalent PIP(2) showed stronger interaction with peptides than monovalent lipids.
• Spatially homogeneous membranes showed weak reduction in peptide mobility.
• Heterogeneous monovalent lipid distributions induced peptide drift, dependent on complex charge.

Conclusions:

• The formation of a lipid shell around peptides influences their lateral mobility.
• Peptide drift induced by heterogeneous lipid distributions may affect protein localization in signaling pathways.
• This phenomenon could be relevant in cell signaling events altering local anionic lipid densities.