Abstract
We use Monte Carlo simulations to investigate the interactions between cationic semiflexible polymer chains and a model fluid lipid monolayer composed of charge-neutral phosphatidyl-choline (PC), tetravalent anionic phosphatidylinositol 4,5-bisphosphate (PIP2), and univalent anionic phosphatidylserine (PS) lipids. In particular, we explore how chain rigidity and polymer concentration influence the spatial rearrangement and mobility heterogeneity of the monolayer under the conditions where the cationic polymers anchor on the monolayer. We find that the anchored cationic polymers only sequester the tetravalent PIP2 lipids at low polymer concentrations, where the interaction strength between the polymers and the monolayer exhibits a non-monotonic dependence on the degree of chain rigidity. Specifically, maximal anchoring occurs at low polymer concentrations, when the polymer chains have an intermediate degree of rigidity, for which the PIP2 clustering becomes most enhanced and the mobility of the polymer/PIP2 complexes becomes most reduced. On the other hand, at sufficiently high polymer concentrations, the anchoring strength decreases monotonically as the chains stiffen—a result that arises from the pronounced competitions among polymer chains. In this case, the flexible polymers can confine all PIP2 lipids and further sequester the univalent PS lipids, whereas the stiffer polymers tend to partially dissociate from the monolayer and only sequester smaller PIP2 clusters with greater mobilities. We further illustrate that the mobility gradient of the single PIP2 lipids in the sequestered clusters is sensitively modulated by the cooperative effects between anchored segments of the polymers with different rigidities. Our work thus demonstrates that the rigidity and concentration of anchored polymers are both important parameters for tuning the regulation of anionic lipids.
Highlights
A deep understanding of the interactions between peripheral cationic bio-macromolecules and anionic lipid membranes is crucial for many cellular activities [1,2], including ion-channel activation, vesicle trafficking, cellular apoptosis, enzyme activation, etc
We further extend our study to the anchoring of multiple cationic polymers with variable chain stiffness onto a fluid mixed lipid monolayer, and we explicitly explore how chain rigidity and polymer concentration affect the properties of macromolecule/membrane complexes with a particular focus on the sequestration and mobility heterogeneity of the anionic lipids
We investigate the mobility of the sequestered anionic lipid clusters underneath the anchored anchored cationic polymers
Summary
A deep understanding of the interactions between peripheral cationic bio-macromolecules and anionic lipid membranes is crucial for many cellular activities [1,2], including ion-channel activation, vesicle trafficking, cellular apoptosis, enzyme activation, etc. The complex coacervates of charged macromolecules and liposomes have been extensively studied via a variety of experimental techniques [1,4,6,7,8,9,10], such as X-ray scattering, transmission electron microscopy, fluorescence resonance energy transfer measurements, etc These studies have demonstrated that the anchored charged macromolecules can adjust the fraction of free anionic lipids and cause the mobility heterogeneity of the membrane through the electrostatic sequestration of the anionic lipids, thereby offering useful information for the development of biological and medical applications [11,12,13,14,15,16]. We further extend our study to the anchoring of multiple cationic polymers with variable chain stiffness onto a fluid mixed lipid monolayer, and we explicitly explore how chain rigidity and polymer concentration affect the properties of macromolecule/membrane complexes with a particular focus on the sequestration and mobility heterogeneity of the anionic lipids.
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