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In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations. We apply this framework to explore the link between trafficking, signaling in the tumor microenvironment, and cell fate. At each stage, we aim to connect the results of our predictions with cellular experiments.
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http://dx.doi.org/10.1016/bs.mie.2024.03.028 | DOI Listing |
Arch Med Res
September 2025
Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan. Electronic address:
Background: Atherosclerosis, a leading cause of cardiovascular disease (CVD) mortality worldwide, is characterized by dysregulated lipid metabolism and unresolved inflammation. Macrophage-derived foam cell formation and apoptosis contribute to plaque formation and vulnerability. Elevated serum galectin-3 (Gal-3) levels are associated with increased CVD risk, and Gal-3 in plaques is strongly associated with macrophages.
View Article and Find Full Text PDFChannels (Austin)
December 2025
Biorheology Research Laboratory, Faculty of Health, Griffith University, Gold Coast, Australia.
The hallmarks of mechanosensitive ion channels have been observed for half a century in various cell lines, although their mechanisms and molecular identities remained unknown until recently. Identification of the bona fide mammalian mechanosensory Piezo channels resulted in an explosion of research exploring the translation of mechanical cues into biochemical signals and dynamic cell morphology responses. One of the Piezo isoforms - Piezo1 - is integral in the erythrocyte (red blood cell; RBC) membrane.
View Article and Find Full Text PDFPhysiology (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 Leukoc Biol
September 2025
Laboratory of Immunobiology and Ionic Transport Regulation, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Villa de San Sebastián, 28045 Colima, México.
Ion channels are integral membrane proteins which facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the phospholipase C (PLCγ)/inositol-1,4,5-triphospate receptor (IP3R)/calcium release-activated calcium channel (CRAC) axis.
View Article and Find Full Text PDFSci Transl Med
September 2025
Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.
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