Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin

How forces and mechanics influence and regulate living cells remains elusive. Mechanomemory, the response to a mechanical perturbation that persists after the perturbation is removed, is believed to be a key to understanding the impact of forces and mechanics on cell functions. Recently, our lab has...

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Main Authors: Fazlur Rashid, Elvis Njoki, Sadia Amin Kabbo, Ning Wang
Format: Article
Language:English
Published: AIP Publishing LLC 2025-06-01
Series:APL Bioengineering
Online Access:http://dx.doi.org/10.1063/5.0253046
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author Fazlur Rashid
Elvis Njoki
Sadia Amin Kabbo
Ning Wang
author_facet Fazlur Rashid
Elvis Njoki
Sadia Amin Kabbo
Ning Wang
author_sort Fazlur Rashid
collection DOAJ
description How forces and mechanics influence and regulate living cells remains elusive. Mechanomemory, the response to a mechanical perturbation that persists after the perturbation is removed, is believed to be a key to understanding the impact of forces and mechanics on cell functions. Recently, our lab has demonstrated the presence of mechanomemory that lasts for ∼30 min after applying external stress via integrins. Herein, we test the hypothesis that applications of short intermittent episodes of stress exert long-term effects on mechanomemory via the process of mechanotransduction. An Arginine-Glycine-Aspartic acid (RGD)-peptides-coated 4-μm magnetic bead was bound to the integrin receptors to apply stresses to the surface of a Chinese Hamster Ovary cell. At the same stress magnitude and frequency (15 Pa at 0.3 Hz), multiple cycles of externally applied intermittent 2 or 10 min stresses with 15 min intervals, 10 min stresses with 10 min intervals, or a 30 min stress plus a 30 min load-free interval increased nuclear translocation of YAP (Yes-Associated Protein) and Ctgf gene expression, like that by a 60 min continuous stress, but a 30 min continuous stress did not. Short durations of intermittent stresses increased F-actin in the cytoplasm, which coincided with the elevated YAP translocation. Inhibiting F-actin or actomyosin but not microtubules blocked stress-induced YAP translocation to the nucleus. Cells on soft substrates translocate more YAP than on stiff substrates after external load release. These results highlight the impact of multiple intermittent stresses-induced cytoplasmic mechanomemory on cell biological functions via YAP translocation.
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spelling doaj-art-734eb5cf0c8f4ca78bf49fbe22a958292025-08-20T03:31:06ZengAIP Publishing LLCAPL Bioengineering2473-28772025-06-0192026107026107-1110.1063/5.0253046Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actinFazlur Rashid0Elvis Njoki1Sadia Amin Kabbo2Ning Wang3The Institute for Mechanobiology, Northeastern University, Boston, Massachusetts 02115, USAThe Institute for Mechanobiology, Northeastern University, Boston, Massachusetts 02115, USAThe Institute for Mechanobiology, Northeastern University, Boston, Massachusetts 02115, USAThe Institute for Mechanobiology, Northeastern University, Boston, Massachusetts 02115, USAHow forces and mechanics influence and regulate living cells remains elusive. Mechanomemory, the response to a mechanical perturbation that persists after the perturbation is removed, is believed to be a key to understanding the impact of forces and mechanics on cell functions. Recently, our lab has demonstrated the presence of mechanomemory that lasts for ∼30 min after applying external stress via integrins. Herein, we test the hypothesis that applications of short intermittent episodes of stress exert long-term effects on mechanomemory via the process of mechanotransduction. An Arginine-Glycine-Aspartic acid (RGD)-peptides-coated 4-μm magnetic bead was bound to the integrin receptors to apply stresses to the surface of a Chinese Hamster Ovary cell. At the same stress magnitude and frequency (15 Pa at 0.3 Hz), multiple cycles of externally applied intermittent 2 or 10 min stresses with 15 min intervals, 10 min stresses with 10 min intervals, or a 30 min stress plus a 30 min load-free interval increased nuclear translocation of YAP (Yes-Associated Protein) and Ctgf gene expression, like that by a 60 min continuous stress, but a 30 min continuous stress did not. Short durations of intermittent stresses increased F-actin in the cytoplasm, which coincided with the elevated YAP translocation. Inhibiting F-actin or actomyosin but not microtubules blocked stress-induced YAP translocation to the nucleus. Cells on soft substrates translocate more YAP than on stiff substrates after external load release. These results highlight the impact of multiple intermittent stresses-induced cytoplasmic mechanomemory on cell biological functions via YAP translocation.http://dx.doi.org/10.1063/5.0253046
spellingShingle Fazlur Rashid
Elvis Njoki
Sadia Amin Kabbo
Ning Wang
Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
APL Bioengineering
title Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
title_full Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
title_fullStr Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
title_full_unstemmed Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
title_short Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin
title_sort mechanomemory after short episodes of intermittent stresses induces yap translocation via increasing f actin
url http://dx.doi.org/10.1063/5.0253046
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AT sadiaaminkabbo mechanomemoryaftershortepisodesofintermittentstressesinducesyaptranslocationviaincreasingfactin
AT ningwang mechanomemoryaftershortepisodesofintermittentstressesinducesyaptranslocationviaincreasingfactin