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In confluent cell monolayers, patterns of cell forces and motion are systematically altered near topological defects in cell shape. In turn, defects have been proposed to alter cell density, extrusion, and invasion, but it remains unclear how the defects form and how they affect cell forces and motion. Here, we studied +1/2 defects, and, in contrast to prior studies, we observed the concurrent occurrence of both tail-to-head and head-to-tail defect motion in the same cell monolayer. We quantified the cell velocities, the tractions at the cell-substrate interface, and the stresses within the cell layer near +1/2 defects. Results revealed that both traction and stress are sources of activity and dissipation within the epithelial cell monolayer, with the direction of motion of +1/2 defects depending on whether energy is injected by stresses or tractions. Interestingly, patterns of motion, traction, stress, and energy injection near +1/2 defects existed before defect formation, suggesting that defects form as a result of spatially coordinated patterns in cell forces and motion. These findings introduce a new focus, on coordinated patterns of force and motion that lead to defect formation and motion.
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http://dx.doi.org/10.1016/j.newton.2025.100231 | DOI Listing |
Biomed Chromatogr
October 2025
Department of Rehabilitation, Nan'ao People's Hospital, Shenzhen, China.
Chrysotobibenzyl, a bioactive ingredient from Dendrobium chrysotoxum, exhibits potent anti-tumor activity. However, its metabolic profiles remain unelucidated. This study aimed to disclose the metabolic fates of chrysotobibenzyl using human liver fractions.
View Article and Find Full Text PDFNature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Department of Pediatrics and Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: erid
Fetal brain anomalies identified by prenatal ultrasound and/or magnetic resonance imaging represent a considerable healthcare burden with ∼1-2/1,000 live births. To identify the underlying etiology, trio prenatal exome sequencing or genome sequencing (ES/GS) has emerged as a comprehensive diagnostic paradigm with a reported diagnostic rate up to ∼32%. Here, we report five unrelated families with six affected individuals that presented neuroanatomical, craniofacial, and skeletal anomalies, all harboring rare, bi-allelic deleterious variants in SNAPIN, which encodes SNARE-associated protein.
View Article and Find Full Text PDFCurr Biol
September 2025
Institut Curie, PSL Research University, CNRS UMR 144, 75005 Paris, France.
Epithelia are specialized and selective tissue barriers that separate the organism's interior from the external environment. Among adult tissues, the gut epithelium must withstand microbial and biochemical insults but also mechanical stresses imposed by luminal contents and gastrointestinal motility. In addition, the continuous renewal of the intestinal epithelium creates tension that must be withstood by cell-cell junctions and the actomyosin cytoskeleton to preserve barrier integrity.
View Article and Find Full Text PDFPhys Rev Lett
August 2025
University of Chinese Academy of Sciences, Kavli Institute for Theoretical Sciences, Beijing 100190, China.
We consider correlation functions of two maximal giant gravitons and two light 1/2-BPS (Bogomol'nyi-Prasad-Sommerfield) operators in 4D N=4 SYM (super Yang-Mills). Viewed as two-point correlators in the presence of a zero-dimensional defect, they can be completely fixed at strong coupling using analytic bootstrap techniques. We determine all infinitely such correlators for arbitrary light 1/2-BPS operators and find that the result can be repackaged into a simple generating function thanks to a hidden higher-dimensional symmetry.
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