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Download fileEffects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers
journal contribution
posted on 2017-01-23, 00:00 authored by Xiaozheng Duan, Yang Zhang, Liangyi Li, Ran Zhang, Mingming Ding, Qingrong Huang, Wen-Sheng Xu, Tongfei Shi, Lijia AnWe 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 PIP2 lipids and drag the PIP2 clusters
to migrate on the monolayer. The polymer/PIP2 binding is
found to be drastically enhanced by increasing the polymer ionization
fraction, which causes the PIP2 lipids to form into larger
clusters and reduces the mobility of the polymer/PIP2 complexes.
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
PIP2 cluster. The desorbed segments of the anchored polymers
exhibit a faster mobility on the membrane, whereas the PIP2 clusters are closely restrained by the limited adhering cationic
segments of anchoring polymers. We further demonstrate that the PIP2 molecules display a hierarchical mobility in the PIP2 clusters, which is regulated by the synergistic effect between
the cationic segments of the polymers. The PS lipids sequester in
the vicinity of the polymer/PIP2 complexes if the tetravalent
PIP2 lipids 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.