Versatile formation of supported lipid bilayers from bicellar mixtures of phospholipids and capric acid

Abstract

Originally developed for the structural biology field, lipid bicelle nanostructures composed of longand short-chain phospholipid molecules have emerged as a useful interfacial science tool to fabricate two-dimensional supported lipid bilayers (SLBs) on hydrophilic surfaces due to ease of sample preparation, scalability, and versatility. To improve SLB fabrication prospects, there has been recent interest in replacing the synthetic, short-chain phospholipid component of bicellar mixtures with naturally abundant fatty acids and monoglycerides, i.e., lauric acid and monocaprin. Such options have proven successful under specific conditions, however, there is room for devising more versatile fabrication options, especially in terms of overcoming lipid concentration-dependent SLB formation limitations. Herein, we investigated SLB fabrication by using bicellar mixtures consisting of long-chain phospholipid and capric acid, the latter of which has similar headgroup and chain length properties to lauric acid and monocaprin, respectively. Quartz crystal microbalance-dissipation, epifluorescence microscopy, and fluorescence recovery after photobleaching experiments were conducted to characterize lipid concentration-dependent bicelle adsorption onto silicon dioxide surfaces. We identified that uniform-phase SLB formation occurred independently of total lipid concentration when the ratio of long-chain phospholipid to capric acid molecules ("q-ratio") was 0.25 or 2.5, which is superior to past results with lauric acid-and monocaprin-containing bicelles in which cases lipid concentration-dependent behavior was observed. Together, these findings demonstrate that capric acid-containing bicelles are versatile tools for SLB fabrication and highlight how the molecular structure of bicelle components can be rationally finetuned to modulate self-assembly processes at solid-liquid interfaces. Bicelles are an important class of membrane-mimicking lipid nanostructures that self-assemble from mixtures of long-and short-chain phospholipids under appropriate processing conditions 1,2. Also known as lipid nanodisks 3 or bilayered mixed micelles 4,5 , bicelles can exist in a wide range of morphologies (e.g., perforated sheets and wormlike micelles) depending on parameters such as temperature, q-ratio (long-to short-chain phospholipid molar ratio), total lipid concentration, and lipid composition, and are widely conceptualized as two-dimensional disks whereby long-chain phospholipids constitute a planar lipid bilayer surface and the short-chain phospholipids form a rimmed edge around the bilayer 6-12. Since they can exhibit magnetic alignment in some cases, bicellar disks have long been used in the nuclear magnetic resonance spectroscopy field as membrane protein hosts 4,13-16. In the interfacial science field, bicelles have also proven to be useful as a lipid nanostructure to fabricate supported lipid bilayers (SLBs), which are extensively used in applications such as biosensors and micropatterned arrays 17-25. Indeed, bicelle adsorption onto...

Nanoarchitectured air-stable supported lipid bilayer incorporating sucrose–bicelle complex system

“…Intriguingly, SLBs formed in 10–30 wt% sucrose condition showed comparable diffusivity values to the control sample (0 wt% sucrose) (Fig. 3 B), which demonstrate that they agree well with literature values reported for high-quality SLBs with the diffusivity of 2.2–2.6 μm 2 /s [ 37 , 60 , 61 ]. In addition, the SLBs from 10 to 30 wt% sucrose exhibited high mobile fractions of > 85% (Fig.…”

Membrane Models and Experiments Suitable for Studies of the Cholesterol Bilayer Domains

“…Sut at al. [ 82 ] have successfully formed SLBs using bicelles with mixtures containing up to a 30 mol% Chol concentration. However, when increasing the Chol content further, some bicelles did not rupture, so incomplete SLBs formed with adsorbed unruptured bicelles.…”

Lipid coating technology: A potential solution to address the problem of sticky containers and vanishing drugs

“…While long‐chain phospholipids are abundantly available, one initially limiting aspect of the bicelle method was the need to include short‐chain phospholipids, which are far less common and relatively expensive; a commonly used one is 1,2‐dihexanoyl‐ sn ‐glycero‐3‐phosphocholine (DHPC) 29,53–55 . However, recent progress has demonstrated the potential to use bicellar nanostructures composed of long‐chain phopsholipids and low cost, widely available free fatty acids or monoglycerides to effectively and affordably fabricate SLBs 56–58 . Hence, bicelles are an attractive tool to mass‐manufacture SLB coatings on account of robust fabrication, simple processing, and low‐cost materials.…”

“…29,[53][54][55] However, recent progress has demonstrated the potential to use bicellar nanostructures composed of long-chain phopsholipids and low cost, widely available free fatty acids or monoglycerides to effectively and affordably fabricate SLBs. [56][57][58] Hence, bicelles are…”