We develop and apply new approaches to understand membrane proteins in their native biological environment — from individual protein complexes to tissues, disease and proteome-wide molecular interactions.
Capturing Membrane Proteins in Their Native State: Membrane proteins are difficult to study outside the lipid bilayer, where conventional detergents can disrupt their structure, interactions, and associated lipids. Our laboratory developed peptide-based membrane mimetics that provide alternative ways to extract and stabilize membrane proteins. Peptidiscs surround the membrane-exposed surface of proteins after extraction, creating stable, water-soluble particles that adapt to proteins of different sizes and shapes. More recently, Peptergents have extended this approach by enabling membrane proteins to be extracted directly from biological membranes without conventional detergents. Together, these technologies provide a foundation for studying membrane proteins from individual purified complexes to entire membrane proteomes.
KEY PUBLICATIONS
The Peptidisc, a simple method for stabilizing membrane proteins in detergent-free solution. Carlson ML, Young JW, Zhao Z, Fabre L, Jun D, Li J, Li J, Dhupar HS, Wason I, Mills AT, Beatty JT, Klassen JS, Rouiller I, Duong F. eLife. 2018;7:e34085. doi:10.7554/eLife.34085.
New approach for membrane protein reconstitution into peptidiscs and basis for their adaptability to different proteins. Angiulli G, Dhupar HS, Suzuki H, Wason IS, Duong Van Hoa F, Walz T. eLife. 2020;9:e53530. doi:10.7554/eLife.53530.
PEPTERGENT: A Peptide-Based Reagent for Detergent-Free Extraction of Membrane Proteins and Purification of Membrane Proteomes. Antony F, Bhattacharya A, Duong van Hoa F. Bio-protocol. 2026;16(10):e5700. doi:10.21769/BioProtoc.5700.
A detergent-free workflow for native membrane proteomics using Peptergents. Antony F, Bhattacharya A, Aoki H, Babu M, Duong van Hoa F. bioRxiv. 2026.08.12.744532. doi:10.64898/2026.08.12.744532. Preprint.
Discovering Native Membrane Protein Networks: Membrane proteins rarely function in isolation. They assemble into complexes and larger molecular networks that control transport, signaling, metabolism, and many other cellular processes. Yet these interactions can be difficult to detect because membrane disruption and prolonged exposure to detergents can cause fragile protein assemblies to dissociate. By combining membrane mimetics with biochemical fractionation, affinity purification, and quantitative mass spectrometry, we can capture membrane protein complexes and identify their interaction partners directly from biological membranes. Our early Peptidisc interactome studies demonstrated that thousands of membrane protein interactions could be reconstructed from native membrane preparations. These approaches have since allowed us to discover and stabilize fragile membrane assemblies that are difficult to observe using conventional detergent-based methods. Together, this provides a way to move beyond studying individual membrane proteins toward understanding how they are organized into functional molecular networks.
KEY PUBLICATIONS
Profiling the Escherichia coli membrane protein interactome captured in Peptidisc libraries.
Carlson ML, Stacey RG, Young JW, Wason IS, Zhao Z, Rattray DG, Scott N, Kerr CH, Babu M, Foster LJ, Duong Van Hoa F. eLife. 2019;8:e46615. doi:10.7554/eLife.46615.Development of a Method Combining Peptidiscs and Proteomics to Identify, Stabilize, and Purify a Detergent-Sensitive Membrane Protein Assembly.
Young JW, Wason IS, Zhao Z, Kim S, Aoki H, Phanse S, Rattray DG, Foster LJ, Babu M, Duong van Hoa F. J Proteome Res. 2022;21(7):1748–1758. doi:10.1021/acs.jproteome.2c00129.Antony F, Bhattacharya A, Aoki H, Babu M, Duong van Hoa F. A detergent-free workflow for native membrane proteomics using Peptergents. bioRxiv. 2026.08.12.744532. doi:10.64898/2026.08.12.744532. Preprint.
From Tissues to Disease: Membrane proteins define how cells communicate with their environment and perform many of the specialized functions of different tissues. Changes in these proteins are also closely associated with disease, yet the membrane proteome remains considerably less explored than its soluble counterpart. We use membrane mimetics together with quantitative mass spectrometry to investigate membrane proteins directly from mammalian cells and tissues. These approaches allow us to compare membrane proteomes across organs and identify receptors, transporters, enzymes, and other membrane proteins associated with tissue-specific functions. We are now applying these methods to disease models to understand how membrane proteomes are remodeled by metabolic, neurological, and other pathological changes — and how these changes respond to pharmacological intervention. This brings membrane proteomics from descriptive protein identification toward understanding disease mechanisms, biological pathways, and potential therapeutic targets.
KEY PUBLICATIONS
A Peptidisc-Based Survey of the Plasma Membrane Proteome of a Mammalian Cell. Zhao Z, Khurana A, Antony F, Young JW, Hewton KG, Brough Z, Zhong T, Parker SJ, Duong van Hoa F. Mol Cell Proteomics. 2023;22(8):100588. doi:10.1016/j.mcpro.2023.100588.
Capture of the Mouse Organ Membrane Proteome Specificity in Peptidisc Libraries. Antony F, Brough Z, Zhao Z, Duong van Hoa F. J Proteome Res. 2024;23(2):857–867. doi:10.1021/acs.jproteome.3c00825.
Sensitive Profiling of Mouse Liver Membrane Proteome Dysregulation Following a High-Fat and Alcohol Diet Treatment. Antony F, Brough Z, Orangi M, Al-Seragi M, Aoki H, Babu M, Duong van Hoa F. Proteomics. 2024;24(23–24):e202300599. doi:10.1002/pmic.202300599.
Comparative Evaluation of Solid-phase and Membrane Mimetic Strategies in Membrane Proteome Coverage and Disease-State Analysis. Antony F, Bhattacharya A, Aoki H, Jandu RS, Abdualkader AM, Al Batran R, Babu M, Duong van Hoa F. Mol Cell Proteomics. 2026;25(2):101496. doi:10.1016/j.mcpro.2025.101496.
Membrane Proteome Remodeling in Female APP/PS1 Mice Following M1 Muscarinic Receptor Modulation Revealed by Peptidisc-Enabled DIA-MS. Bhattacharya A, Antony F, Aoki H, Babu M, Ferguson SSG, Abd-Elrahman KS, Duong van Hoa F. J Proteome Res. 2026;25(6):3136–3148. doi:10.1021/acs.jproteome.6c00140.`
Membrane Protein Regulation and Ligand Interactions
Membrane proteins constantly interact with lipids, metabolites, ions, and small molecules that can alter their stability, conformation, and function. Understanding these interactions is important both for fundamental membrane biology and for discovering how drugs act on membrane protein targets. We developed Membrane Mimetic Thermal Proteome Profiling (MM-TPP) to investigate these interactions across entire membrane proteomes. By measuring changes in protein stability following exposure to a ligand, MM-TPP can reveal both specific target interactions and broader effects on membrane protein organization. We are using this approach to study interactions with metabolites, lipids, and pharmacologically active compounds, moving from individual membrane protein–ligand pairs toward proteome-wide maps of membrane protein regulation. More recently, we have extended MM-TPP to investigate how the lipid environment itself shapes membrane protein stability, providing a new way to explore the relationship between membrane composition and protein function.
KEY PUBLICATIONS
Capture of endogenous lipids in peptidiscs and effect on protein stability and activity.
Jandu RS, Yu H, Zhao Z, Le HT, Kim S, Huan T, Duong van Hoa F.
iScience. 2024;27(4):109382. doi:10.1016/j.isci.2024.109382.Membrane-mimetic thermal proteome profiling (MM-TPP) toward mapping membrane protein-ligand dynamic interactions.
Jandu RS, Bhattacharya A, Antony F, Al-Seragi M, Aoki H, Babu M, Duong van Hoa F.
eLife. 2025;14:RP104549. doi:10.7554/eLife.104549.Membrane Mimetic-Thermal Proteome Profiling Reveals Broad, Sequence-Independent Membrane Protein Stabilization by Cholesteryl Hemisuccinate.
Bhattacharya A, Clunie S, Antony F, Chen Y, Aoki H, Babu M, Duong van Hoa F.
bioRxiv. 2026.08.17.745344. doi:10.64898/2026.08.17.745344. Preprint.