Role of molecular tilt in thermal fluctuations of lipid membranes

Abstract

Long-wavelength thermal fluctuations of lipid membranes are adequately described by the Helfrich elastic model. On the other hand, fluctuations of wavelengths comparable with bilayer thickness exhibit significant deviations from the prediction of the elastic model and are typically assumed to be dominated by microscopic surface tension due to protrusion of lipid molecules into the solvent. We present evidence that the short-wavelength modes of a lipid membrane are dominated by fluctuations of the tilt of lipid molecules with respect to the membrane normal rather than the microscopic surface tension. We obtain an expression for the spectral intensity of the thermal membrane fluctuations by appealing to the Hamm-Kozlov model, which accounts for both membrane bending and lipid tilt contributions to the total membrane energy but neglects the contributions of the microscopic surface tension. The tilt and the bending fluctuations obtained from our coarse-grained molecular dynamics simulations of a dipalmitoylphosphatidylcholine lipid bilayer show good agreement with the theory. Furthermore, the obtained tilt and bending moduli are in close agreement with experimentally determined values. The magnitude of the microscopic protrusion tension estimated from our simulations is significantly smaller than that of the tilt modulus. These results indicate that the membrane fluctuations can be adequately described by a macroscopic elastic model down to scales of interlipid distance provided one accounts for the tilt fluctuations.

Bilayer-thickness-mediated interactions between integral membrane proteins

“…However, additional structural properties of the lipid bilayer, such as lipid tilt [72][73][74][75][76][77][78], may have a more substantial effect on bilayer-mediated protein interactions. Moreover, integral membrane proteins may tilt to reduce hydrophobic mismatch, as suggested by Monte Carlo and molecular dynamics simulations [119,120].…”

“…(3) and the corresponding "zeroth-order" models [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] capturing curvature-and fluctuation-mediated protein interactions absorb the molecular details of lipids and membrane proteins into effective material parameters. To provide a more detailed description of bilayer-protein interactions, a number of extensions and refinements of these models have been developed [44,45,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86]. For instance, the effect of bilayer-protein interactions on the elastic properties of lipid bilayers can be captured [44,81,82,86] by allowing for spatial variations in the values of the elastic bilayer parameters.…”

“…The minimal model in Eq. (3) can be extended in a variety of ways to account for more detailed properties of lipid bilayers including lipid tilt [48,[75][76][77][78][79], lipid intrinsic curvature [39-42, 45, 70, 71], inhomogeneous deformation of lipid volume and effects of Gaussian curvature on protein-induced bilayer deformations [45,70,71], asymmetric bilayer thickness deformations [45,70,71,80], and protein-induced local modulation of bilayer elastic properties [44,[81][82][83][84][85][86].…”

“…The classic elasticity theory of protein-induced lipid bilayer deformations can be extended in various ways [44,45,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] to account for detailed molecular properties of lipids such as lipid tilt and lipid intrinsic curvature [39][40][41][42]48], yielding additional modes of bilayermediated protein interactions. Theoretical studies of bilayer-mediated protein interactions have largely focused on idealized (often cylindrical or conical) protein shapes which do not correspond to any particular membrane protein, and proteins at large d. In contrast, bilayer-mediated protein interactions at small d are most relevant for the crowded environment provided by cell membranes [3,[21][22][23], while modern structural biology suggests a rich picture of membrane protein shape with experimental surveys of the protein content in various cell membranes [21,23,87] indicating great diversity in the oligomeric states and symmetries of membrane proteins.…”

Thermal fluctuations and bending rigidity of bilayer membranes

“…22 The effects of the molecular tilt have also been introduced. 28,29 These studies claim that the phospholipid tilt may be more relevant than the protrusions. Using this approach it was shown that the simulation data can be very well fitted, even for membrane lateral lengths of a few nanometers.…”