Surface Interactions Stabilize Lipids with High Intrinsic Curvature in Bacteria-Mimicking Planar Lipid Bilayers
Year: 2026
Type: article
Abstract: Supported lipid bilayers are key platforms for measuring membrane-implicated drug interactions, disease mechanisms, and biological processes. Bacterial model membranes are a particularly high-value target but present unique fabrication challenges due to the high intrinsic curvature of their constituent lipids, notably phosphatidylethanolamine (PE). Here, we report a fundamental role for headgroup chemistry in stabilizing lipids with high intrinsic curvature on flat solid surfaces and predictive guidelines for tuning the preparative lipid concentration depending on surface chemistry. Building on recent developments in solvent-exchange techniques, we fully automate the production of bilayers comprised of a biologically relevant ratio of PE and the anionic lipid phosphatidylglycerol (PG). Neutron reflectometry measurements are performed to compare the structure of these membranes with that of bilayers containing phosphatidylcholine, the benchmark lipid for supported lipid bilayers. Bilayers are characterized in terms of both completeness and bilayer-substrate distance, which is indicative of adsorption strength, on neutral oxide, acidic, and basic surfaces. Despite their high intrinsic curvature, bacterial model membranes are found to interact strongly with all surfaces. We attribute this surprising observation to hydrogen bonding with substrate surface moieties. These observations lead to a unified predictive model of the physicochemical forces of bilayer adhesion to solid surfaces, enabling a future of high-throughput production of custom bilayers for complex assays and drug discovery.
Source: Langmuir
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: PURPOSE: THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO ENHANCE THE DEVELOPMENT OF NEXT GENERATION NEUTRON INSTRUMENTATION, ADVANCE SCIENTIFIC RESEARCH, AND BUILD AN EDUCATIONAL PIPELINE SKILLED IN NEUTRON SCATTERING AS A LONG-TERM NATIONAL INVESTMENT.ACTIVITIES TO BE PERFORMED: TO PROVIDE TECHNICAL EXPERTISE AND OPERATIONS SUPPORT FOR NEUTRON INSTRUMENTATION; DEVELOPMENT WORK TO PROVIDE BOTH NEW AND TO IMPROVE NEUTRON MEASUREMENT CAPABILITIES; SUPPORT FIRST-TIME NCNR FACILITY USERS FOR BEAMTIME PROPOSALS; SUPPORT EDUCATIONAL AND OUTREACH PROGRAMS; SCIENTIFIC AND TECHNICAL DISSEMINATION OF RESEARCH RESULTS; SUPPORT AND DEVELOP ADVANCED NEUTRON METROLOGY INSTRUMENTATION AND METHODS AND ASSIST THE BROADER U.S. NEUTRON RESEARCH COMMUNITY IN ACADEMIA, INDUSTRY, AND GOVERNMENT SERVICE. EXPECTED OUTCOMES: IT IS ANTICIPATED THAT THE WORK OUTLINED IN THIS PROPOSAL WILL SUPPORT THE NEUTRON SPECTROSCOPY AND SCATTERING FACILITIES BY INTEGRATING POSTDOCS AND STUDENTS, IN COLLABORATION WITH NCNR STAFF, TO PROVIDE TECHNICAL EXPERTISE AND OPERATIONAL SUPPORT TO FACILITY USERS AND SCIENTISTS. DEVELOPMENT OF NEW INSTRUMENTS, SAMPLE ENVIRONMENTS, SOFTWARE, AND ENGINEERING SUPPORT TO IMPROVE THE NEUTRON MEASUREMENT CAPABILITIES AND TO INSTITUTE AN EDUCATIONAL & OUTREACH WORKFORCE.INTENDED BENEFICIARIES: U.S. SCIENTIFIC COMMUNITY AND THE GENERAL PUBLIC.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS., UNIVERSITY OF MARYLAND / NIST CENTER FOR NEUTRON RESEARCH JOINT PROGRAM FOR THE ADVANCEMENT OF NEUTRON SCATTERING AND SPECTROSCOPY, G7349965092, PURPOSE: THE PURPOSE OF THIS GRANT IS TO ADVANCE NEUTRON-BASED MEASUREMENTS TO SUPPORT KEY INDUSTRIES OF THE US ECONOMY. TO SUPPORT THE PROPOSED COLLABORATION TO MEET EXISTING AND EMERGING NEEDS OF STAKEHOLDERS IN BIOTECHNOLOGY AND BIOMANUFACTURING.ACTIVITIES TO BE PERFORMED: DEVELOPMENT IN SAMPLE PREPARATION AND ANALYSIS, AS WELL AS CUTTING-EDGE AND VITAL FUNDAMENTAL RESEARCH PROBLEMS THAT MUST BE ADDRESSED IN BIOTECHNOLOGY AND BIOMANUFACTURING. THIS WILL IMPACT NOVICE USERS OF NEUTRON SCATTERING WHILE AT THE SAME TIME CREATING INNOVATIVE MEASUREMENT AND ANALYSIS MODALITIES FOR FUTURE APPLICATIONS. EXPAND THE RESEARCH PROGRAMS IN NEUTRONS AND, SEPARATELY, ARTIFICIAL INTELLIGENCE AND PROVIDE NEW EDUCATIONAL OPPORTUNITIES TO UNDERGRADUATE, GRADUATE, AND POST-GRADUATE STUDENTS OF CARNEGIE MELLON.EXPECTED OUTCOMES: INNOVATIONS IN SAMPLE PREPARATION AND ANALYSIS, AS WELL AS CUTTING-EDGE AND VITAL FUNDAMENTAL RESEARCH PROBLEMS. THIS WILL IMPACT NOVICE USERS OF NEUTRON SCATTERING WHILE AT THE SAME TIME CREATING INNOVATIVE MEASUREMENT AND ANALYSIS MODALITIES FOR FUTURE APPLICATIONS.INTENDED BENEFICIARIES: CARNEGIE MELLON UNIVERSITY WILL BENEFIT BY ADVANCED SCIENTIFIC CAPACITY TO BETTER EDUCATE STUDENTS AND ADVANCE SCIENCE THROUGH INSTRUMENT DEVELOPMENT PROJECTS. THE GENERAL PUBLIC BY GAINING ACCESS TO STATE-OF-THE-ART MEASUREMENT TECHNIQUES THROUGH THE NCNR GENERAL USER PROGRAM AND NEW THERAPEUTICS THAT ARE ANTICIPATED TO RESULT FROM THESE CAPABILITIES.SUBRECIPIENT ACTIVITIES: THE RECIPIENT DOES NOT INTEND TO SUBAWARD FUNDS.
OpenAlex ID: W7225397862