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Poloxamers consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) segments can protect cell membranes against various forms of stress. We investigated the role of the hydrophobic block chemistry on polymer/membrane binding and cell membrane protection by comparing a series of poly(butylene oxide)--PEO (PBO--PEO) copolymers to poloxamer analogues, using a combination of pulsed-field-gradient (PFG) NMR experiments and a lactate dehydrogenase (LDH) cell assay. We found that the more hydrophobic PBO--PEO copolymers bound more significantly to model liposomes composed of 1-palmitol-2-oleoyl-glycero-3-phosphocholine (POPC) compared to poly(propylene oxide) (PPO)/PEO copolymers. However, both classes of polymers performed similarly when compared by an LDH assay. These results present an important comparison between polymers with similar structures but with different binding affinities. They also provide mechanistic insight as enhanced polymer/lipid membrane binding did not directly translate to increased cell protection in the LDH assay, and therefore, additional factors need to be considered when trying to achieve greater membrane protection efficacy.
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http://dx.doi.org/10.1021/acs.biomac.1c01661 | DOI Listing |
Physiology (Bethesda)
September 2025
Departments of Ophthalmology and Medicine, Stanford Cardiovascular Institute, Stanford University, Palo Alto, CA 94304.
Canonical activation of G-protein coupled receptors (GPCRs) by hormone binding occurs at the plasma membrane, resulting in the diffusion of second messengers to intracellular effector sites throughout the cell. In contrast, recent evidence suggests that functional GPCRs can induce signaling from distinct intracellular domains, contributing to specificity in signaling. Functional adrenergic receptors have been identified at intracellular sites in the cardiac myocyte such as endosomes, the sarcoplasmic reticulum, the Golgi and the inner nuclear membrane.
View Article and Find Full Text PDFJ Infect Dis
September 2025
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA USA.
Sequestration of Plasmodium falciparum-infected erythrocytes (IE) in the microvasculature is a major virulence determinant. While the sequestration of mature stage parasites (trophozoite and schizonts) to vascular endothelium is well established, the conditions that promote ring-stage IE sequestration is less understood. Here, we observed in ring-stage parasites that febrile exposure increased transcript levels of several exported parasite genes involved in the trafficking of the P.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
State Key Laboratory of Green Biomanufacturing, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
High-mobility group box protein 1 (HMGB1) is a chromatin-associated nonhistone protein widely distributed in the nucleus of eukaryotic cells. It is transported extracellularly as a proinflammatory mediator or late warning protein to induce immune and inflammatory reactions upon stimuli such as microbial infection. Here, we have found that HMGB1 directly interacts with bacterial DNA analogue CpG-A in the extracellular environment to undergo liquid-liquid phase separation (LLPS) via its positively charged DNA-binding domain.
View Article and Find Full Text PDFPhytopathology
September 2025
Guizhou University, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Huaxi District, Guiyang, Guizhou Province of China, Guiyang, China, 550025;
Osthole exhibits strong inhibitory activity against phytopathogenic fungi; however, its antifungal mechanism remains unclear. This study assessed osthole's inhibitory effects on several phytopathogenic fungi, revealing a half-maximal effective concentration of 70.03 μg/ml against the hyphal growth of .
View Article and Find Full Text PDFElife
September 2025
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, United States.
The microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer's disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained.
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