Protein diffusion on charged membranes: A dynamic mean-field model describes time evolution and lipid reorganization

George Khelashvili*, Harel Weinstein, Daniel Harries

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


As charged macromolecules adsorb and diffuse on cell membranes in a large variety of cell signaling processes, they can attract or repel oppositely charged lipids. This results in lateral membrane rearrangement and affects the dynamics of protein function. To address such processes quantitatively we introduce a dynamic mean-field scheme that allows self-consistent calculations of the equilibrium state of membrane-protein complexes after such lateral reorganization of the membrane components, and serves to probe kinetic details of the process. Applicable to membranes with heterogeneous compositions containing several types of lipids, this comprehensive method accounts for mobile salt ions and charged macromolecules in three dimensions, as well as for lateral demixing of charged and net-neutral lipids in the membrane plane. In our model, the mobility of membrane components is governed by the diffusion-like Cahn-Hilliard equation, while the local electrochemical potential is based on nonlinear Poisson-Boltzmann theory. We illustrate the method by applying it to the adsorption of the anionic polypeptide poly-Lysine on negatively charged lipid membranes composed of binary mixtures of neutral and monovalent lipids, or onto ternary mixtures of neutral, monovalent, and multivalent lipids. Consistent with previous calculations and experiments, our results show that at steady-state multivalent lipids (such as PIP2), but not monovalent lipid (such as phosphatidylserine), will segregate near the adsorbing macromolecules. To address the corresponding diffusion of the adsorbing protein in the membrane plane, we couple lipid mobility with the propagation of the adsorbing protein through a dynamic Monte Carlo scheme. We find that due to their higher mobility dictated by the electrochemical potential, multivalent lipids such as PIP2 more quickly segregate near oppositely charged proteins than do monovalent lipids, even though their diffusion constants may be similar. The segregation, in turn, slows protein diffusion, as lipids introduce an effective drag on the motion of the adsorbate. In contrast, monovalent lipids such as phosphatidylserine only weakly segregate, and the diffusions of protein and lipid remain largely uncorrelated.

Original languageAmerican English
Pages (from-to)2580-2597
Number of pages18
JournalBiophysical Journal
Issue number7
StatePublished - Apr 2008

Bibliographical note

Funding Information:
G.K. and H.W. are supported by National Institutes of Health grants No. P01 DA012408 and No. P01 DA012923. D.H. thanks the Israeli Council of Higher Education for its support through an Alon Fellowship, as well as a Career Development Award from the Hebrew University Intramural Research Fund. The Fritz Haber Research Center is supported by the Minerva Foundation, Munich, Germany.


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