Coupling of Lipid Phase Behavior and Protein Oligomerization in a Lattice Model of Raft Membranes
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arXiv
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| Natura: | Preprint |
| Pubblicazione: |
2025
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| _version_ | 1866917516013469696 |
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| author | Basu, Subhadip Farago, Oded |
| author_facet | Basu, Subhadip Farago, Oded |
| contents | Membrane proteins often form dimers and higher-order oligomers whose stability and spatial organization depend sensitively on their lipid environment. To investigate the physical principles underlying this coupling, we employ a lattice Monte Carlo model of ternary lipid mixtures that exhibit liquid-disordered ($L_d$) and liquid-ordered ($L_o$) phase coexistence. In this framework, proteins are represented as small membrane inclusions with tunable nearest neighbor interactions with both lipids and other proteins, allowing us to examine how protein-lipid affinity competes with protein-protein interactions and lipid-lipid demixing. We find that the balance of these interactions controls whether proteins remain dispersed, assemble into small oligomers, or form large stable clusters within $L_o$ domains, and that increasing the protein concentration further promotes coarsening of the ordered phase. To incorporate ligand-regulated activation, we extend the model to a kinetic Monte Carlo scheme in which proteins stochastically switch between inactive and active states with distinct affinities. The inverse switching rate, relative to the time required for a protein to diffuse across the characteristic size of the $L_o$ domains, governs the aggregation behavior. Rapid switching yields only transient small oligomers, slow switching reproduces the static limit with persistent large clusters, and intermediate rates produce broad cluster-size distributions. These results highlight the interplay between lipid phase organization, protein-lipid affinity, and activation dynamics in regulating membrane protein oligomerization, a coupling that is central to signal transduction and membrane organization in living cells. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2511_06949 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Coupling of Lipid Phase Behavior and Protein Oligomerization in a Lattice Model of Raft Membranes Basu, Subhadip Farago, Oded Soft Condensed Matter Biological Physics Membrane proteins often form dimers and higher-order oligomers whose stability and spatial organization depend sensitively on their lipid environment. To investigate the physical principles underlying this coupling, we employ a lattice Monte Carlo model of ternary lipid mixtures that exhibit liquid-disordered ($L_d$) and liquid-ordered ($L_o$) phase coexistence. In this framework, proteins are represented as small membrane inclusions with tunable nearest neighbor interactions with both lipids and other proteins, allowing us to examine how protein-lipid affinity competes with protein-protein interactions and lipid-lipid demixing. We find that the balance of these interactions controls whether proteins remain dispersed, assemble into small oligomers, or form large stable clusters within $L_o$ domains, and that increasing the protein concentration further promotes coarsening of the ordered phase. To incorporate ligand-regulated activation, we extend the model to a kinetic Monte Carlo scheme in which proteins stochastically switch between inactive and active states with distinct affinities. The inverse switching rate, relative to the time required for a protein to diffuse across the characteristic size of the $L_o$ domains, governs the aggregation behavior. Rapid switching yields only transient small oligomers, slow switching reproduces the static limit with persistent large clusters, and intermediate rates produce broad cluster-size distributions. These results highlight the interplay between lipid phase organization, protein-lipid affinity, and activation dynamics in regulating membrane protein oligomerization, a coupling that is central to signal transduction and membrane organization in living cells. |
| title | Coupling of Lipid Phase Behavior and Protein Oligomerization in a Lattice Model of Raft Membranes |
| topic | Soft Condensed Matter Biological Physics |
| url | https://arxiv.org/abs/2511.06949 |