Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an electrostatic model and experimental results.
Direct fluorescence digital imaging microscopy observations demonstrate that a basic peptide corresponding to the effector region of the myristoylated alanine-rich C kinase substrate (MARCKS) self-assembles into membrane domains enriched in the acidic phospholipids phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). We show here that pentalysine, which corresponds to the first five residues of the MARCKS effector region peptide and binds to membranes through electrostatic interactions, also forms domains enriched in PS and PIP2. We present a simple model of domain formation that represents the decrease in the free energy of the system as the sum of two contributions: the free energy of mixing of neutral and acidic lipids and the electrostatic free energy. The first contribution is always positive and opposes domain formation, whereas the second contribution may become negative and, at low ionic strength, overcome the first contribution. Our model, based on Gouy-Chapman-Stern theory, makes four predictions: 1) multivalent basic ligands, for which the membrane binding is a steep function of the mole fraction of acidic lipid, form domains enriched in acidic lipids; domains break up at high concentrations of either 2) basic ligand or 3) monovalent salt; and 4) if multivalent anionic lipids (e.g., PIP2) are present in trace concentrations in the membrane, they partition strongly into the domains. These predictions agree qualitatively with experimental data obtained with pentalysine and spermine, another basic ligand.
Denisov
G
G
Department of Physiology and Biophysics, Health Science Center, SUNY Stony Brook, New York 11794-8661, USA.
Wanaski
S
S
Luan
P
P
Glaser
M
M
McLaughlin
S
S
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives; D000595:Amino Acid Sequence; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry* / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C034296:N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylserine; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D019269:Phosphatidylinositol 4,5-Diphosphate; D010718:Phosphatidylserines; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; C017251:1,2-oleoylphosphatidylcholine; D009327:4-Chloro-7-nitrobenzofurazan