Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
Confinement controls the stochastic onset of single-cell rotation. |
| Συγγραφείς: |
Echeverría-Alar S; Department of Physics, University of California, San Diego, CA 92093., Narasimhan BN; Department of Bioengineering, University of California, San Diego, CA 92093., Fraley SI; Department of Bioengineering, University of California, San Diego, CA 92093., Rappel WJ; Department of Physics, University of California, San Diego, CA 92093. |
| Πηγή: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Sep 15; Vol. 123 (37), pp. e2602259123. Date of Electronic Publication: 2026 Sep 10. |
| Τύπος έκδοσης: |
Journal Article |
| Γλώσσα: |
English |
| Στοιχεία περιοδικού: |
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| Imprint Name(s): |
Original Publication: Washington, DC : National Academy of Sciences |
| Ιατρικοί όροι (MeSH): |
Epithelial Cells*/cytology , Epithelial Cells*/physiology , Models, Biological*, Extracellular Matrix/physiology ; Extracellular Matrix/metabolism ; Stochastic Processes ; Humans ; Rotation ; Single-Cell Analysis ; Cell Movement ; Cell Line |
| Περίληψη: |
Single cells confined by the extracellular matrix can exhibit rotational motion, yet the physical mechanisms underlying its onset and persistence remain unclear. Here, we address this gap with a cellular phase field model that couples cell deformation, cell polarization governed by stochastic excitable dynamics, and confinement. We identify the confinement strength as a bifurcation parameter determining three regimes: Strong confinement prevents rotation through spatial constraints, intermediate confinement induces stochastic transitions between rotating and nonrotating states, and weak confinement allows persistent rotations. For the intermediate regime, we develop a semi-Markovian renewal process framework that characterizes the stochastic dynamics through dwell time statistics, transition probabilities, and first-passage times. For the weak confinement regime, we reveal that a mechanochemical feedback enables coherent rotations despite internal noise through the reduction of local excitability mediated by mechanical contraction. We formalize this feedback analytically using Kramers escape theory. Experiments on epithelial MCF10A cells in Matrigel demonstrate three types of cell dynamics that recapitulate those observed in each confinement regime. Our results establish a theoretical approach for understanding single-cell rotations under confinement, with implications for controlling single-cell dynamics by tuning extracellular matrix properties. |
| Competing Interests: |
Competing interests statement:S.I.F. is a cofounder, scientific advisor, and equity holder in MelioLabs, Inc.; the interests of this company are unrelated to the findings reported in this paper. S.I.F. is cofounder, director, and equity holder in Serafin Labs, Inc., a company that may have a distant interest in the findings of this work. S.I.F. is an inventor on a patent distantly related to this work. |
| Grant Information: |
PHY 2310496 National Science Foundation (NSF); MCB 2426002 National Science Foundation (NSF); Heroes grant Prebys Foundation Research; 74230063 Agencia Nacional de Investigación y Desarrollo (ANID) |
| Contributed Indexing: |
Keywords: ECM confinement; actin waves; epithelial cells; mechanochemical feedback; stochastic excitable systems |
| Entry Date(s): |
Date Created: 20260910 Date Completed: 20260910 Latest Revision: 20260919 |
| Update Code: |
20260919 |
| PubMed Central ID: |
PMC13584169 |
| DOI: |
10.1073/pnas.2602259123 |
| PMID: |
42721088 |
| Βάση Δεδομένων: |
MEDLINE |