Influence of the Nature of the Lipid Building Blocks on the Second-Order Nonlinear Optical Responses of an Embedded Di-8-ANEPPS Probe

Abstract

The extensive collection of lipids found in cell membranes is justified by the fact that each lipid contributes to their overall structure, dynamics, and properties and so to the biological processes taking place within them. It also showcases that, in order to deepen our understanding of membranes, we need to have a tool to differentiate lipid bilayers of varying composition. In this work, we investigate a suite of single-component saturated glycerophospholipids varying only in their headgroup structure by analyzing the second harmonic generation (SHG) nonlinear optical (NLO) response of a probe, di-8-ANEPPS, embedded into the membranes. The seven hydrophilic heads chosen (phosphatidylcholine (PC), phosphatidylethanolamine (PE), diaglycerol (GL), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidyc acid (PA)) represent all the major headgroups that are part of mammalian plasma membranes and provide an assortment of neutral, zwiterrionic, and charged species. First, molecular dynamics simulations revealed that the lipidic arrangement is strongly sensitive to the nature of the hydrophilic head and less to the variety in the hydrophobic region. Membranes exhibiting drastically opposite structural properties can be pointed out: 1,2-dihexadecanoyl-rac-glycerol (DPGL) is the thickest and most ordered and aligned system, whereas 1,2-diacyl-sn-glycero-3-phospho-(1′-sn-glycerol) (DPPG) is thinnest and least ordered and aligned system. The structural analyses are then confronted with the molecular NLO responses, β, computed at the time-dependent density functional theory (TDDFT) level. As the orientation of the chromophore is impacted by the various degrees of order within the lipid bilayers, the diagonal component of the β tensor parallel to the bilayer normal, βZZZ, is as well. In the end, this computational approach provides insights into the link between lipid building blocks and the NLO responses of the embedded dye.

Investigating the Influence of the Lipid Structure on the Global Membrane Organization: Effect of the Fatty Acids

“…[73] Each membrane is composed of 128 lipids (64 in each leaflet) that differ in chemical structure. As a complement to our previous article, [53] which focuses on varying the nature of the polar head of the lipids, the present work spotlights the second building block of lipids, i. e. their fatty acid chains. For this, the diaglycerol backbone with a choline head was kept identical and the length of the fatty acids and/or the number of (un)saturation(s) were modified, ranging from chains of 10-22 carbon atoms and 0-2 unsaturation(s) per fatty acid.…”

Multimillion Atom Simulations of Di-8-ANEPPS Chromophores Embedded in a Model Plasma Membrane: Toward the Investigation of Realistic Dyed Cell Membranes

“…On the other hand, for the SM family, the results are not really affected by the complexity of the system and differ by only ∼5 Å 2 compared to a full SM bilayer. 31 The least asymmetric lipid (SSM) is also the most densely packed. This is explained by its small tilt angle (∼16°).…”

“…However, the study of biological-like membranes is still incomplete. Often only a few different lipid species are considered at a time, − even for larger lipid bilayers (LBs). − Moreover, computer simulations have replaced all-atom (AA) descriptions with coarse-grain (CG) approaches in an attempt to limit the computational cost of large systems. , This makes it possible to study membrane structural changes on larger size and time scales, such as raft formation, , lipid flip-flop, , or membrane–protein interactions. , CG approaches are well suited in these cases but not when the investigation requires detailed information about the flexibility, conformation, or geometry of the system components. This atomic resolution is especially necessary in multiscale and multistep approaches, where molecular dynamics (MD) simulations are performed first, followed by quantum mechanical (QM) calculations to address optical properties.…”

“…Previous MD studies by our group have focused on a single molecule of di-8-ANEPPS embedded in simple model membranes featuring single-component lipid bilayers . It has been shown that the lipid organization is strongly dependent on the nature of the hydrophilic lipid head.…”

Electric-field induced second harmonic generation responses of push–pull polyenic dyes: experimental and theoretical characterizations

“…As recently reviewed, 27 this MD + QM scheme was formerly employed to investigate ion pairs in solution, 23,24,28 but also more complex systems such as organic nanoparticles, 29 selfassembled monolayers, 30,31 and stained lipid bilayers. [32][33][34] Here, MD simulations carried out on the reference D3/iodine complex bring key information on the average position of the iodide anion with respect to the organic chromophore, as well as on the effect of dynamical structural fluctuations on the NLO properties. Then, systematic TD-DFT calculations performed on the whole set of systems provide a rationale to experimental data and allow to establish precise relationships between the structure of the dye and the magnitude of the second-and third-order contributions to the EFISH intensity.…”