Bilayer lipid membrane formation on surface assemblies with sparsely distributed tethers

A combined computational and experimental study of small unilamellar vesicle (SUV) fusion on mixed self-assembled monolayers (SAMs) terminated with different deuterated tether moieties (-(CD2)(7)CD3 or -(CD2)(15)CD3) is reported. Tethered bilayer lipid membrane (tBLM) formation of synthetic 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine was initially probed on SAMs with controlled tether (d-alkyl tail) surface densities and lateral molecular packing using quartz crystal microbalance with dissipation monitoring (QCM-D). Long time-scale coarse-grained molecular dynamics (MD) simulations were then employed to elucidate the mechanisms behind the interaction between the SUVs and the different phases formed by the -(CD2)(7)CD3 and -(CD2)(15)CD3 tethers. Furthermore, a series of real time kinetics was recorded under different osmotic conditions using QCM-D to determine the accumulated lipid mass and for probing the fusion process. It is shown that the key factors driving the SUV fusion and tBLM formation on this type of surfaces involve tether insertion into the SUVs along with vesicle deformation. It is also evident that surface densities of the tethers as small as a few mol% are sufficient to obtain stable tBLMs with a high reproducibility. The described sparsely tethered tBLM system can be advantageous in studying different biophysical phenomena, such as membrane protein insertion, effects of receptor clustering, and raft formation.

Automated summary

This study combines computational and experimental methods to investigate the fusion of small unilamellar vesicles (SUVs) on mixed self-assembled monolayers (SAMs) with different deuterated tether moieties. Initially, tethered bilayer lipid membrane (tBLM) formation was studied on SAMs with controlled tether surface densities using quartz crystal microbalance with dissipation monitoring (QCM-D). Molecular dynamics simulations were then used to understand the interaction mechanisms between the SUVs and different phases formed by the deuterated tethers. Real-time kinetics were recorded using QCM-D under different osmotic conditions to determine lipid mass accumulation and fusion process. The study reveals the key factors for SUV fusion and tBLM formation on the surfaces, and shows the advantages of the sparsely tethered tBLM system in studying various biophysical phenomena.