Abstrakt
Lipid nanodiscs are nanometric bilayer patches enveloped by confining structures, commonly composed of membrane scaffolding proteins (MSPs). Because they create native-like membrane environments, nanodiscs have become a powerful embedding media for structural determination of transmembrane proteins using cryo-electron microscopy or nuclear magnetic resonance.
However, although it is well appreciated that the material properties of lipid bilayers can impact the conformational state of the embedded protein, the effect of confinement on lipid nanodisc environment has not been fully scrutinized. Here, we utilized a combined computational and theoretical approach.
Using our previously developed methodology, we extracted the locally varying elastic moduli of various nanodiscs from MD simulations. We find that lipids in nanodiscs are stiffer than in their corresponding macroscopic bilayers, and moreover, their material properties vary spatially within them.
For small MSP1 nanodiscs, the stiffness decreases radially, with their center being TILDE OPERATOR+D912-3 times stiffer than in bulk bilayers. Larger nanodiscs show milder spatial changes of moduli that depend on lipid identity.
The elastic moduli locally correlate with other properties, such as thickness and area-per-lipid. Applying a continuum elastic model to bilayers of finite size accurately captured the nanodiscs shape.
The model indicates that nanodisc shape is sensitive to its size, lipid density, and tilt and thickness at the lipid-MSP contact. Under matching physical parameters, the nanodiscs shape found in MD simulations is quantitatively reproduced by the model.
We demonstrate how the bending rigidity can be extracted from the membrane shape by fitting the model to yield the observed membrane shape. For larger nanodiscs, the fitted bending moduli match the value and local variations of those determined from simulations using our computational methodology.
Our results should allow to guide the future development of nanodiscs as controlled environments with known properties for proteins.