Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization

Ting Ching Wang; Samere Abolghasemzade; Brendan P. McKee; Ishita Singh; Kavya Pendyala; Mohammad Mohajeri; Hailee Patel; Aakansha Shaji; Anna L. Kersey; Kajol Harsh; Simran Kaur; Christina R. Dollahon; Sasanka Chukkapalli; Pushkar P. Lele; Daniel E. Conway; Akhilesh K. Gaharwar; Richard B. Dickinson; Tanmay P. Lele

doi:10.1038/s41467-024-54577-4

Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization

Ting Ching Wang, Samere Abolghasemzade, Brendan P. McKee, Ishita Singh, Kavya Pendyala, Mohammad Mohajeri, Hailee Patel, Aakansha Shaji, Anna L. Kersey, Kajol Harsh, Simran Kaur, Christina R. Dollahon, Sasanka Chukkapalli, Pushkar P. Lele, Daniel E. Conway, Akhilesh K. Gaharwar, Richard B. Dickinson, Tanmay P. Lele

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31 Scopus citations

Abstract

Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.

Original language	English (US)
Article number	10151
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-54577-4
State	Published - Dec 2024

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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Wang, T. C., Abolghasemzade, S., McKee, B. P., Singh, I., Pendyala, K., Mohajeri, M., Patel, H., Shaji, A., Kersey, A. L., Harsh, K., Kaur, S., Dollahon, C. R., Chukkapalli, S., Lele, P. P., Conway, D. E., Gaharwar, A. K., Dickinson, R. B., & Lele, T. P. (2024). Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization. Nature Communications, 15(1), Article 10151. https://doi.org/10.1038/s41467-024-54577-4

Wang, TC, Abolghasemzade, S, McKee, BP, Singh, I, Pendyala, K, Mohajeri, M, Patel, H, Shaji, A, Kersey, AL, Harsh, K, Kaur, S, Dollahon, CR, Chukkapalli, S, Lele, PP, Conway, DE, Gaharwar, AK, Dickinson, RB & Lele, TP 2024, 'Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization', Nature Communications, vol. 15, no. 1, 10151. https://doi.org/10.1038/s41467-024-54577-4

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title = "Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization",

abstract = "Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.",

author = "Wang, \{Ting Ching\} and Samere Abolghasemzade and McKee, \{Brendan P.\} and Ishita Singh and Kavya Pendyala and Mohammad Mohajeri and Hailee Patel and Aakansha Shaji and Kersey, \{Anna L.\} and Kajol Harsh and Simran Kaur and Dollahon, \{Christina R.\} and Sasanka Chukkapalli and Lele, \{Pushkar P.\} and Conway, \{Daniel E.\} and Gaharwar, \{Akhilesh K.\} and Dickinson, \{Richard B.\} and Lele, \{Tanmay P.\}",

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doi = "10.1038/s41467-024-54577-4",

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AU - Wang, Ting Ching

AU - Abolghasemzade, Samere

AU - McKee, Brendan P.

AU - Singh, Ishita

AU - Pendyala, Kavya

AU - Mohajeri, Mohammad

AU - Patel, Hailee

AU - Shaji, Aakansha

AU - Kersey, Anna L.

AU - Harsh, Kajol

AU - Kaur, Simran

AU - Dollahon, Christina R.

AU - Chukkapalli, Sasanka

AU - Lele, Pushkar P.

AU - Conway, Daniel E.

AU - Gaharwar, Akhilesh K.

AU - Dickinson, Richard B.

AU - Lele, Tanmay P.

PY - 2024/12

Y1 - 2024/12

N2 - Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.

AB - Extracellular matrix (ECM) stiffness influences cancer cell fate by altering gene expression. Previous studies suggest that stiffness-induced nuclear deformation may regulate gene expression through YAP nuclear localization. We investigated the role of the nuclear lamina in this process. We show that the nuclear lamina exhibits mechanical threshold behavior: once unwrinkled, the nuclear lamina is inextensible. A computational model predicts that the unwrinkled lamina is under tension, which is confirmed using a lamin tension sensor. Laminar unwrinkling is caused by nuclear flattening during cell spreading on stiff ECM. Knockdown of lamin A/C eliminates nuclear surface tension and decreases nuclear YAP localization. These findings show that nuclear deformation in cells conforms to the nuclear drop model and reveal a role for lamin A/C tension in controlling YAP localization in cancer cells.

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Matrix stiffness drives drop like nuclear deformation and lamin A/C tension-dependent YAP nuclear localization

Abstract

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