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  • Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wan, Y., Hudson, R., Smith, J., Forman-Kay, J. D., Ditlev, J. A. 2025; 122 (11): e2424470122

    Abstract

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of chloride ions, dehydration of cell surfaces, and subsequent damage to airway and ductal organs. Beyond its function as a chloride channel, interactions between CFTR, epithelium sodium channel, and solute carrier (SLC) transporter family membrane proteins and cytoplasmic proteins, including calmodulin and Na+/H+ exchanger regulatory factor-1 (NHERF-1), coregulate ion homeostasis. CFTR has also been observed to form mesoscale membrane clusters. However, the contributions of multivalent protein and lipid interactions to cluster formation are not well understood. Using a combination of computational modeling and biochemical reconstitution assays, we demonstrate that multivalent interactions with CFTR protein binding partners, calcium, and membrane cholesterol can induce mesoscale CFTR cluster formation on model membranes. Phosphorylation of the intracellular domains of CFTR also promotes mesoscale cluster formation in the absence of calcium, indicating that multiple mechanisms can contribute to CFTR cluster formation. Our findings reveal that coupling of multivalent protein and lipid interactions promotes CFTR cluster formation consistent with membrane-associated biological phase separation.

    View details for DOI 10.1073/pnas.2424470122

    View details for Web of Science ID 001459456400001

    View details for PubMedID 40063811

    View details for PubMedCentralID PMC11929494

  • Dynamics of Deep Eutectic Mixtures of Tetraethylammonium Halides/Ethylene Glycol Investigated with Ultrafast Infrared Spectroscopy. The journal of physical chemistry. B Pan, J., Carter-Fenk, K. A., Hung, S. T., Dao, N., Smith, J. N., Fayer, M. D. 2025

    Abstract

    Health and environmental risks posed by volatile organic solvents create an incentive to develop safer, less volatile solvents with the appropriate functionality. Deep eutectic solvents and other low-volatility organic mixtures offer a highly tunable alternative through a mixture composition selection. However, a significant gap exists in understanding the relationship between molecular-level properties and the resulting solvation and transport properties. Using ultrafast infrared (IR) polarization-selective pump-probe (lifetimes and orientational relaxation) spectroscopy, we investigated the dynamics of 1:3 molar mixtures of tetraethylammonium bromide (TEABr) and chloride (TEACl) with ethylene glycol (EG) and of pure EG using the anionic vibrational probe, the CN stretch of SeCN-. The very high salt concentrations are in many respects analogous to water-in-salt solutions, e.g., LiBr and LiCl. These ion/water mixtures can have extremely high ratios of ions to solvating neutral molecules, similar to the 1:3TEABr and 1:3TEACl mixtures studied here. In 1:3TEABr/EG and 1:3TEACl/EG solutions, there are far too few EGs to solvate the ions. Therefore, like water-in-salt, 1:3TEABr/EG and 1:3TEACl/EG solutions will have solvent-separated ion pairs, contact ion pairs, and large ion/EG clusters, forming extended ion/solvent networks. The orientational dynamics experiments on 1:3TEABr/EG and 1:3TEACl/EG show striking similarities to experiments from the literature on 1:4 LiBr and LiCl aqueous solutions, even though the cations and solvents in the deep eutectic mixtures are vastly different.

    View details for DOI 10.1021/acs.jpcb.4c08739

    View details for PubMedID 40014810