Stabilizing microtubules increases acute cellular injury at high strain rates.
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| Titel: | Stabilizing microtubules increases acute cellular injury at high strain rates. |
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| Autoren: | Kang G; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada., Webster E; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada., Delgado D; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada., Holahan MR; Department of Neuroscience, Carleton University, Ottawa, ON, Canada., Banton R; U.S. Army Research Laboratory, Aberdeen, Maryland., Petel OE; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada., Harris AR; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada. Electronic address: andrew.harris3@carleton.ca. |
| Quelle: | Biophysical journal [Biophys J] 2025 Dec 02; Vol. 124 (23), pp. 4321-4334. Date of Electronic Publication: 2025 Oct 21. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-0086 (Electronic) Linking ISSN: 00063495 NLM ISO Abbreviation: Biophys J Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, MA : Cell Press Original Publication: New York, Published by Rockefeller University Press [etc.] for the Biophysical Society. |
| MeSH-Schlagworte: | Microtubules*/metabolism , Microtubules*/drug effects , Stress, Mechanical*, Humans ; tau Proteins/metabolism ; Phosphorylation/drug effects ; Cell Line, Tumor ; Paclitaxel/pharmacology ; Brain Injuries, Traumatic/pathology ; Brain Injuries, Traumatic/metabolism ; Cell Membrane/metabolism ; Cell Membrane/drug effects |
| Abstract: | Mechanical strain is a key contributor to mild traumatic brain injury (mTBI), yet the impact of varying strain magnitudes and strain rates on cellular function and disease remain poorly understood. In this study, we examined acute membrane damage responses to mechanical strain in SH-SY5Y cells and the modulatory roles of Tau phosphorylation and microtubule stability in the context of mTBI. Using a custom cell-stretching system, we found that increased MT stability, induced by paclitaxel, increases acute membrane damage, while MT depolymerization via nocodazole reduces it. Interestingly, overexpression of wild-type Tau exacerbates injury under strain. Pharmacological treatments with phosphatase and kinase inhibitors that are used as therapeutics for neurological disorders further revealed that Tau phosphorylation modulates mTBI outcomes, highlighting a complex interplay between Tau modification and microtubule stability. These findings advance our understanding of neuronal mechanobiology and suggest potential therapeutic targets for mitigating TBI-induced damage. (Copyright © 2025 Biophysical Society. All rights reserved.) |
| Substance Nomenclature: | 0 (tau Proteins) P88XT4IS4D (Paclitaxel) |
| Entry Date(s): | Date Created: 20251022 Date Completed: 20251203 Latest Revision: 20251204 |
| Update Code: | 20251205 |
| DOI: | 10.1016/j.bpj.2025.10.024 |
| PMID: | 41121664 |
| Datenbank: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstract: | Mechanical strain is a key contributor to mild traumatic brain injury (mTBI), yet the impact of varying strain magnitudes and strain rates on cellular function and disease remain poorly understood. In this study, we examined acute membrane damage responses to mechanical strain in SH-SY5Y cells and the modulatory roles of Tau phosphorylation and microtubule stability in the context of mTBI. Using a custom cell-stretching system, we found that increased MT stability, induced by paclitaxel, increases acute membrane damage, while MT depolymerization via nocodazole reduces it. Interestingly, overexpression of wild-type Tau exacerbates injury under strain. Pharmacological treatments with phosphatase and kinase inhibitors that are used as therapeutics for neurological disorders further revealed that Tau phosphorylation modulates mTBI outcomes, highlighting a complex interplay between Tau modification and microtubule stability. These findings advance our understanding of neuronal mechanobiology and suggest potential therapeutic targets for mitigating TBI-induced damage.<br /> (Copyright © 2025 Biophysical Society. All rights reserved.) |
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| ISSN: | 1542-0086 |
| DOI: | 10.1016/j.bpj.2025.10.024 |