Tuning membrane thickness fluctuations in model lipid bilayers.

Membrane thickness fluctuations have been associated with a variety of critical membrane phenomena, such as cellular exchange, pore formation, and protein binding, which are intimately related to cell functionality and effective pharmaceuticals. Therefore, understanding how these fluctuations are controlled can remarkably impact medical applications involving selective macromolecule binding and efficient cellular drug intake. Interestingly, previous reports on single-component bilayers show almost identical thickness fluctuation patterns for all investigated lipid tail-lengths, with similar temperature-independent membrane thickness fluctuation amplitude in the fluid phase and a rapid suppression of fluctuations upon transition to the gel phase. Presumably, in vivo functions require a tunability of these parameters, suggesting that more complex model systems are necessary. In this study, we explore lipid tail-length mismatch as a regulator for membrane fluctuations. Unilamellar vesicles of an equimolar mixture of dimyristoylphosphatidylcholine and distearoylphosphatidylcholine molecules, with different tail-lengths and melting transition temperatures, are used as a model system for this next level of complexity. Indeed, this binary system exhibits a significant response of membrane dynamics to thermal variations. The system also suggests a decoupling of the amplitude and the relaxation time of the membrane thickness fluctuations, implying a potential for independent control of these two key parameters.

Lipid bilayers and membrane dynamics: insight into thickness fluctuations.

Thickness fluctuations have long been predicted in biological membranes but never directly observed experimentally. Here, we utilize neutron spin echo spectroscopy to experimentally reveal such fluctuations in a pure, fully saturated, phosphocholine lipid bilayer system. These fluctuations appear as an excess in the dynamics of undulation fluctuations. Like the bending rigidity, the thickness fluctuations change dramatically as the lipid transition temperature is crossed, appearing to be completely suppressed below the transition. Above the transition, the relaxation rate is on the order of 100 ns and is independent of temperature. The amplitude of the thickness fluctuations is 3.7 Å ± 0.7 Å, which agrees well with theoretical calculations and molecular dynamics simulations. The dependence of the fluctuations on lipid tail lengths is also investigated and determined to be minimal in the range of 14 to 18 carbon tails.