Spatial Rearrangement and Mobility Heterogeneity of an Anionic Lipid Monolayer Induced by the Anchoring of Cationic Semiflexible Polymer Chains

Abstract

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 (PIP 2 ), 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 PIP 2 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 PIP 2 clustering becomes most enhanced and the mobility of the polymer/PIP 2 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 PIP 2 lipids and further sequester the univalent PS lipids, whereas the stiffer polymers tend to partially dissociate from the monolayer and only sequester smaller PIP 2 clusters with greater mobilities. We further illustrate that the mobility gradient of the single PIP 2 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.

Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers

“…To overcome these limitations, novel coarse-grained models were also developed to elucidate the physicochemical natures of the polymer/membrane interactions. ,− These simulations serve as a universal and robust strategy to explore the system on length and time scales beyond the range of chemically detailed models. In previous work, we designed a simple Monte Carlo (MC) model for the complex of a single polyelectrolyte and a mixed monolayer, by which we extensively analyzed the effects of polymerization degree and the rigidity of the polyelectrolyte as well as the influence of the saline solution on the polyelectrolyte/membrane interactions. − Our predictions for some key phenomena associated with these interactions, such as the sequestering and fluidity heterogeneity of the charged lipids as well as the polyelectrolyte anchoring, have been shown to be consistent with recent extensive experimental studies. , …”

“…In previous studies, it has never been assessed systematically how the competitions between the polymers with different synergistic effects of connected cationic segments contribute to the lipid sequestering. To characterize the lipid heterogeneity, we distinguish the “sequestered” charged lipid from the “freely diffusing” one underneath an anchoring polymer using the method described in our previous works. ,,, For each polymer/lipid complex, we define eight interaction zones, with the k th zone indicating the area on the monolayer at a distance of k × d (8.66 Å) from the center of each segment of the polymer, which has proven to be an effective means to detect the properties of the oppositely charged particles bound to a charged polymer . In each MC step, these interaction zones may change their shapes and sizes in accordance with the new conformation of the diffusing anchored polymer.…”

“…Our model includes positively charged polymers and a mobile lipid membrane composed of charge-neutral and negatively charged lipids. We design this MC model on the basis of our previous works − and other references, , which is described below, along with an introduction to the simulation method.…”

“…In every MC step, we perform the trial position updates for all polymer segments and all negatively charged lipids in accordance with the Metropolis algorithm . These trial movements allow us to avoid dynamic trapping of the complex, which otherwise would result in a reliable mobility for both the lipid and the polymers. ,,, We first employ 10 6 MC steps (MCs) athermal relaxation to wipe off the artifact caused by the initial configuration, within which we confine the polymers to move above the monolayer interface. We then employ 2 × 10 6 MCs for the system relaxation, within which the polymers interact with the lipid membrane through U NB in eq .…”

“…Second, we calculate the MSD of the polymers and the anionic lipids to determine lipid sequestration. Although it has proven to be an effective strategy for exploring the dynamic properties of the polymer/membrane complex in equilibrium state, ,,, the MC steps cannot be considered for real-time measurements. Third, we employ the Debye–Hückel approximation to account for in the electrostatic interaction.…”