How lipid composition shapes the nanostructural interaction of tumor biomarker alpha-fetoprotein and bovine serum albumin with model membranes

This study systematically investigated the interactions of the tumor biomarker alpha-fetoprotein (AFP) and bovine serum albumin (BSA) with planar lipid membranes using neutron reflectometry, quartz crystal microbalance with dissipation monitoring, and atomistic molecular dynamics simulations. By exa...

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Main Authors: Barletti, Beatrice (Author) , König, Melanie (Author) , Paracini, Nicoló (Author) , Fragneto, Giovanna (Author) , Alcaraz, Jean-Pierre (Author) , Nelson, Andrew (Author) , Vilgrain, Isabelle (Author) , Martin, Donald K. (Author) , Lolicato, Fabio (Author) , Maccarini, Marco (Author)
Format: Article (Journal)
Language:English
Published: 15 April 2026
In: Journal of colloid and interface science
Year: 2026, Volume: 708, Pages: 1-17
ISSN:1095-7103
DOI:10.1016/j.jcis.2025.139753
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jcis.2025.139753
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0021979725031455
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Author Notes:Beatrice Barletti, Melanie König, Nicoló Paracini, Giovanna Fragneto, Jean-Pierre Alcaraz, Andrew Nelson, Isabelle Vilgrain, Donald K. Martin, Fabio Lolicato, Marco Maccarini

MARC

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520 |a This study systematically investigated the interactions of the tumor biomarker alpha-fetoprotein (AFP) and bovine serum albumin (BSA) with planar lipid membranes using neutron reflectometry, quartz crystal microbalance with dissipation monitoring, and atomistic molecular dynamics simulations. By examining a range of lipid compositions-including charged, neutral, and nanodomain-containing bilayers-we dissected the molecular mechanisms governing protein-membrane interactions. AFP consistently exhibited stronger interactions than BSA. While both proteins showed negligible binding to zwitterionic POPC bilayers, BSA only interacted significantly with negatively charged POPS membranes. In contrast, AFP strongly engaged with both SM/CHOL nanodomains and POPS-containing bilayers, leading to protein incorporation and lipid extraction, respectively. On positively charged DOTAP membranes, AFP formed a stable adsorbed layer. These findings reveal how lipid composition modulates protein adsorption, insertion, and membrane integrity, offering new mechanistic insights into the differential binding affinities of AFP and BSA. The results underscore the importance of protein-lipid interactions in clinical assays for blood tumor biomarkers, as these interactions may influence the formation of protein-lipid complexes and impact detection accuracy. This work may guide the optimization of biosensing strategies, particularly for glycosylated biomarkers, to enhance the sensitivity and reliability of clinical diagnostics. 
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