title: Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers.
abstract: We employed coarse-grained Monte Carlo simulations to investigate a system composed of cationic polymers and a phosphatidyl-choline membrane monolayer, doped with univalent anionic phosphatidylserine (PS) and tetravalent anionic phosphatidylinositol 4,5-bisphosphate (PIP2) lipid molecules. For this system, we consider the conditions under which multiple cationic polymers can anchor onto the monolayer and explore how the concentration and ionization degree of the polymers affect the lateral rearrangement and fluidity of the negatively charged lipids. Our work shows that the anchoring cationic polymers predominantly bind the tetravalent anionic PIP2lipids and drag the PIP2clusters to migrate on the monolayer. The polymer/PIP2binding is found to be drastically enhanced by increasing the polymer ionization fraction, which causes the PIP2lipids to form into larger clusters and reduces the mobility of the polymer/PIP2complexes. As expected, stronger competition effects between anchoring polymers occur at higher polymer concentrations, for which each anchoring polymer partially dissociates from the monolayer and hence sequesters a smaller PIP2cluster. The desorbed segments of the anchored polymers exhibit a faster mobility on the membrane, whereas the PIP2clusters are closely restrained by the limited adhering cationic segments of anchoring polymers. We further demonstrate that the PIP2molecules display a hierarchical mobility in the PIP2clusters, which is regulated by the synergistic effect between the cationic segments of the polymers. The PS lipids sequester in the vicinity of the polymer/PIP2complexes if the tetravalent PIP2lipids cannot sufficiently neutralize the cationic polymers. Finally, we illustrate that the increase in the ionic concentration of the solution weakens the lateral clustering and the mobility heterogeneity of the charged lipids. Our work thus provides a better understanding of the fundamental biophysical mechanism of the concentration gradients and the hierarchical mobility of the anionic lipids in the membrane caused by the cationic polymer anchoring on length and time scales that are generally inaccessible by atomistic models. It also offers insight into the development and design of novel biological applications on the basis of the modulation of signaling lipids.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Duan
authors.affiliation: Northeast Normal University , Changchun 130024, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Liangyi
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Food Science, Rutgers University , 65 Dudley Road, New Brunswick, New Jersey 08901, United States.
authors.forename: Qingrong
authors.identifier: 0000-0001-8637-0229
authors.initials: Q
authors.lastname: Huang
authors.affiliation: James Franck Institute, The University of Chicago , Chicago, Illinois 60637, United States.
authors.forename: Wen-Sheng
authors.identifier: 0000-0002-5442-8569
authors.initials: WS
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Tongfei
authors.identifier: 0000-0002-6763-2200
authors.initials: T
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
authors.forename: Lijia
authors.initials: L
authors.lastname: An
mesh_terms: D000838:Anions; D002412:Cations; D008051:Lipid Bilayers / Q000737:chemistry*; D009010:Monte Carlo Method; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D000838:Anions; D002412:Cations; D008051:Lipid Bilayers; D019269:Phosphatidylinositol 4,5-Diphosphate; D011108:Polymers