TY - JOUR
T1 - Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers
AU - Duan, Xiaozheng
AU - Zhang, Yang
AU - Li, Liangyi
AU - Zhang, Ran
AU - Ding, Mingming
AU - Huang, Qingrong
AU - Xu, Wen Sheng
AU - Shi, Tongfei
AU - An, Lijia
N1 - Funding Information:
This study was funded by the National Natural Science Foundation of China (Nos. 21404103 21234007, 21604086, and 51473168). The authors acknowledge the Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase) and the Computing Center of Jilin Province for their computational support.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/2/9
Y1 - 2017/2/9
N2 - 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 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.
AB - 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 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.
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U2 - 10.1021/acs.jpcb.6b12386
DO - 10.1021/acs.jpcb.6b12386
M3 - Article
C2 - 28110529
AN - SCOPUS:85021425407
VL - 121
SP - 984
EP - 994
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
SN - 1520-6106
IS - 5
ER -