{"entity": "researcher", "timestamp": "2026-08-20T20:50:10.387Z", "family": "Chan", "given": "Sze Ham", "initials": "SH", "orcid": "0000-0002-3235-0852", "affiliations": ["Department of Molecular Physiology and Biological Physics, University of Virginia, USA. il2sy@virginia.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/4854c445b24541adbfcb1a44a1d02305.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/4854c445b24541adbfcb1a44a1d02305"}}, "publications": [{"entity": "publication", "iuid": "4646807d8f2048c7be81d65df4d86d55", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4646807d8f2048c7be81d65df4d86d55.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4646807d8f2048c7be81d65df4d86d55"}}, "title": "Immune cell activation produces locally scrambled foci of plasma membrane lipids.", "authors": [{"family": "Sputay", "given": "Daryna", "initials": "D", "orcid": "0009-0008-9987-5582", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3dedb072e04d447c87728ea160049cf0.json"}}, {"family": "Doktorova", "given": "Milka", "initials": "M", "orcid": "0000-0003-4366-2242", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/791384c319f04584bac8ffb21df7271f.json"}}, {"family": "Chan", "given": "Sze Ham", "initials": "SH", "orcid": "0000-0002-3235-0852", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4854c445b24541adbfcb1a44a1d02305.json"}}, {"family": "Guo", "given": "Emma Han", "initials": "EH"}, {"family": "Wang", "given": "Hong-Yin", "initials": "HY"}, {"family": "Lorent", "given": "Joseph H", "initials": "JH", "orcid": "0000-0002-7537-8521", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c6a5fdf28de42ff8a14a7ae259939cb.json"}}, {"family": "Levental", "given": "Ilya", "initials": "I", "orcid": "0000-0002-1206-9545", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7fe40c2b810348cab78616402d4d1f1f.json"}}, {"family": "Levental", "given": "Kandice R", "initials": "KR", "orcid": "0000-0002-2234-3683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dcde4d3042b349b199c48509444ac8f9.json"}}], "type": "journal article", "published": "2025-08-13", "journal": {"title": "Faraday Discuss", "issn": "1364-5498", "volume": "259", "issue": "0", "pages": "45-59", "issn-l": null}, "abstract": "Most eukaryotic cells maintain a large disparity in lipid compositions between the cytosolic and external leaflets of the plasma membrane (PM) bilayer. This lipid asymmetry is maintained by energy-consuming flippase enzymes that selectively drive phospholipids into the cytosolic leaflet, often against large concentration gradients. Scramblases, activated by intracellular Ca2+ or apoptotic signaling, shuttle phospholipids down their concentration gradient to release lipid asymmetry. Such scrambling is typically evidenced by exposure of phosphatidylserine (PS) to the external leaflet and is associated with many physiological processes, most notably blood clotting and cell death, but also activation of immune cells. Here, we show that both PS and phosphatidylethanolamine (PE) appear on the PM external leaflet following immune receptor-mediated activation of mast cells. We also observe similar effects in T cells. Importantly, in contrast to wholesale release of PM asymmetry induced by calcium ionophores or apoptosis, we show that scrambling in activated immune cells is focal, with small, stable regions of surface exposed PS. These scrambled foci are calcium dependent, have lower lipid packing than their surrounding outer leaflet, and are reversible. These observations of local, transient scrambling during physiological activation of healthy immune cells suggest important roles for the lateral and transbilayer organization of membrane lipids.", "doi": "10.1039/d4fd00205a", "pmid": "40351229", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12067185"}], "notes": [], "created": "2026-08-20T09:27:53.683Z", "modified": "2026-08-20T09:27:53.821Z"}, {"entity": "publication", "iuid": "a2fd7d47dd5148bdb0f5170e51a2f92d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a2fd7d47dd5148bdb0f5170e51a2f92d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a2fd7d47dd5148bdb0f5170e51a2f92d"}}, "title": "Loss of lipid asymmetry facilitates plasma membrane blebbing by decreasing membrane lipid packing.", "authors": [{"family": "Wang", "given": "Hong-Yin", "initials": "HY", "orcid": "0000-0002-8704-2814", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b2e12db192d04321b4c232a49181b8ff.json"}}, {"family": "Rumin", "given": "Alissa", "initials": "A", "orcid": "0009-0006-0314-1353", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/17d45c7578b4489499e15e99132e466d.json"}}, {"family": "Doktorova", "given": "Milka", "initials": "M", "orcid": "0000-0003-4366-2242", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/791384c319f04584bac8ffb21df7271f.json"}}, {"family": "Sputay", "given": "Daryna", "initials": "D", "orcid": "0009-0008-9987-5582", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3dedb072e04d447c87728ea160049cf0.json"}}, {"family": "Chan", "given": "Sze Ham", "initials": "SH", "orcid": "0000-0002-3235-0852", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4854c445b24541adbfcb1a44a1d02305.json"}}, {"family": "Wehman", "given": "Ann M", "initials": "AM", "orcid": "0000-0001-9826-4132", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8575abcc457452d91ec3f61e81616e7.json"}}, {"family": "Levental", "given": "Kandice R", "initials": "KR", "orcid": "0000-0002-2234-3683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dcde4d3042b349b199c48509444ac8f9.json"}}, {"family": "Levental", "given": "Ilya", "initials": "I", "orcid": "0000-0002-1206-9545", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7fe40c2b810348cab78616402d4d1f1f.json"}}], "type": "journal article", "published": "2025-05-13", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "122", "issue": "19", "pages": "e2417145122", "issn-l": "0027-8424"}, "abstract": "Membrane blebs have important roles in cell migration, apoptosis, and intercellular communication through extracellular vesicles (EVs). While plasma membranes (PM) typically maintain phosphatidylserine (PS) on their cytoplasmic leaflet, most blebs have PS exposed on their outer leaflet, revealing that loss of steady-state lipid asymmetry often accompanies PM blebbing. How these changes in PM lipid organization regulate membrane properties and affect bleb formation remains unknown. We confirmed that lipid scrambling through the scramblase TMEM16F is essential for chemically induced membrane blebbing across cell types, with the kinetics of PS exposure being tightly coupled to the kinetics of bleb formation. Measurement of lipid packing with environment-sensitive probes revealed that lipid scrambling changes the physical properties of the PM, reducing lipid packing and facilitating the bilayer bending required for bleb formation. Accordingly, reducing lipid packing of the PM through cholesterol extraction, elevated temperature, or treatment with biological amphiphiles promoted blebbing in the absence of TMEM16F. Consistent with these cellular observations, blebbing in Caenorhabditis elegans embryos measured via EV production was significantly reduced by depleting the TMEM16-homolog ANOH-2. Our findings suggest that changing membrane biophysical properties by lipid scrambling is an important contributor to the formation of blebs and EVs and potentially other cellular processes involving PM deformation.", "doi": "10.1073/pnas.2417145122", "pmid": "40324083", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12088411"}], "notes": [], "created": "2026-08-20T09:31:46.422Z", "modified": "2026-08-20T09:31:46.617Z"}]}