Streamlined Fabrication of Hybrid Lipid Bilayer Membranes on Titanium Oxide Surfaces: A Comparison of One- and Two-Tail SAM Molecules

Abstract

There is broad interest in fabricating cell-membrane-mimicking, hybrid lipid bilayer (HLB) coatings on titanium oxide surfaces for medical implant and drug delivery applications. However, existing fabrication strategies are complex, and there is an outstanding need to develop a streamlined method that can be performed quickly at room temperature. Towards this goal, herein, we characterized the room-temperature deposition kinetics and adlayer properties of one- and two-tail phosphonic acid-functionalized molecules on titanium oxide surfaces in various solvent systems and identified optimal conditions to prepare self-assembled monolayers (SAMs), upon which HLBs could be formed in select cases. Among the molecular candidates, we identified a two-tail molecule that formed a rigidly attached SAM to enable HLB fabrication via vesicle fusion for membrane-based biosensing applications. By contrast, vesicles adsorbed but did not rupture on SAMs composed of one-tail molecules. Our findings support that two-tail phosphonic acid SAMs offer superior capabilities for rapid HLB coating fabrication at room temperature, and these streamlined capabilities could be useful to prepare durable lipid bilayer coatings on titanium-based materials.

Cholesterol-Enriched Hybrid Lipid Bilayer Formation on Inverse Phosphocholine Lipid-Functionalized Titanium Oxide Surfaces

“…We selected two-tail DOCP molecules to form SAMs on TiO 2 because they mimic the basic molecular properties of natural phospholipids and have also proven useful for robust HLB fabrication using vesicle fusion, whereas vesicles adsorbed but did not fully rupture on SAMs composed of one-tail phosphonic acid counterparts [31]. The difference in vesicle fusion efficiency to form the HLB on TiO 2 was previously attributed to differences in SAM packing order [51] between one-tail vs. two-tail SAMs.…”

“…Recently, the use of two-tail inverse phosphocholine (CP) lipids [24][25][26][27] to form SAMs on flat TiO 2 surfaces based on phosphate chemistry (i.e., covalent P-O-Ti bond formation [28]) was also reported and enabled HLB formation across a well-defined set of ionic strength and pH conditions [19,29,30]. Compared to traditional silanization that requires organic solvent, high temperature, and/or a long incubation time (with special surface pretreatment in some cases), the CP lipid attachment scheme on TiO 2 is simpler because it can readily occur in aqueous solution and at room temperature with shorter incubation time and no special surface pretreatment (other than straightforward oxygen plasma treatment) [31]. Therefore, CP-based SAM formation is particularly promising from a fabrication perspective (e.g., to prepare HLBs on biomedically relevant TiO 2 ) and also advantageous from a biomimetic perspective since the attached CP lipids have two hydrocarbon chains (i.e., two tails) per molecule that resembles the structural arrangement of natural phospholipids.…”

“…In this context, HLBs have proven to be a particularly useful model to study cholesterol-related membrane properties since zwitterionic lipid vesicles containing up to ~40 mol% Chol can form the upper leaflet of HLBs on top of single-tail SAMs [20,38,39], whereas vesicles containing only up to ~20 mol% Chol can rupture to form SLBs on SiO 2 surfaces [40,41]. In the two-chain CP SAM context, we have previously demonstrated that upper leaflet formation for HLBs on TiO 2 can be achieved using zwitterionic lipid vesicles that contain a fraction of biotinylated lipids [31], but Chol incorporation into CP SAM-based HLBs has not been attempted. In addition to the vesicle fusion method, the solvent exchange method has excellent potential for Chol incorporation into the upper leaflet of CP SAM-based HLBs because the method can form SLBs on SiO 2 with lipid mixtures containing up to around 63 mol% Chol [40,41].…”

Distinct Binding Properties of Neutravidin and Streptavidin Proteins to Biotinylated Supported Lipid Bilayers: Implications for Sensor Functionalization

“…The highly specific and stable nature of avidin–biotin binding across various environments (e.g., diverse temperature and pH ranges) enables the specific capture and recognition of biomolecules that can be useful for applications such as biosensing, immunoassays, and targeted drug delivery. Moreover, the avidin–biotin interaction has been utilized in nanoscale drug delivery, diagnostic, and biosensor systems due to its favorable merits such as ease of functionalization, efficiency, and stability [ 7 , 8 , 9 , 10 , 11 ]. The main feature of these nanotechnology-focused applications lies in the modification of interacting surfaces with biotin- and/or avidin-conjugated biomolecules, either directly or through multi-step binding sequences and the specifics of the surface modification can be tuned according to the application needs.…”

Crystalline Biomimetic Calcium Phosphate Coating on Mini-Pin Implants to Accelerate Osseointegration and Extend Drug Release Duration for an Orthodontic Application

“…The biological basis for secondary stability is the establishment of a direct connection between MSIs and living bone, also known as osteointegration, during the bone remodeling process [ 6 , 11 , 12 , 13 ]. As a high-quality osteointegration is a critical factor to determine the loading occasion and to ensure the long-term success of MSIs [ 14 ], many efforts have been made to accelerate and enhance the osteointegration of MSIs with an aim to enable an early loading and reduce the failure rate [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”