@article{1e029f73a9b143d091df408e712551fe,
title = "Disrupted stiffness ratio alters nuclear mechanosensing",
abstract = "The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively aged cells had a reduced stiffness ratio, attenuating shear transfer, while the ratio was not altered in a genetic model of accelerated aging. We provide a theoretical framework suggesting that dysregulation of the shear stress response can be uniquely imparted by relative mechanical changes in subcellular compartments.",
keywords = "MAP3: Understanding, biomechanics, biophysics, endothelial cells, mechanobiology, shear stress, soft matter",
author = "Walther, {Brandon K.} and Sears, {Adam P.} and Anahita Mojiri and Reza Avazmohammadi and Jianhua Gu and Chumakova, {Olga V.} and {Rajeeva Pandian}, {Navaneeth Krishna} and Abishai Dominic and Martiel, {Jean Louis} and Yazdani, {Saami K.} and Cooke, {John P.} and Jacques Ohayon and Pettigrew, {Roderic I.}",
note = "Funding Information: Structured illumination microscopy was performed at the Center for Advanced Microscopy, a Nikon Center of Excellence, Department of Integrative Biology & Pharmacology at McGovern Medical School, UTHealth Houston. The authors would like to thank Saurabh Chavan, Xiao Ling, and Emilio Mendiol at Texas A&M University for assisting with the FE simulations; Dr. Manuel Lagache, PhD, from Savoie Mont-Blanc University (Chamb{\'e}ry, France) for help with the FE shear simulations; and Dr. Yohan Payan, PhD, from Laboratory TIMC-CNRS of the University Grenoble-Alpes (Grenoble, France) for helpful discussions. J.O. was funded from February 2020 to September 2020 by Dr. Roderic I. Pettigrew (Welch Chair) on a visiting scholar position at Texas A&M University, Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA. This work was supported by a grant from The Welch Foundation. R.A. was partially supported by NIH grant R00HL138288. This work was additionally supported by grants to J.P.C. (National Institutes of Health [NIH] R01s HL133254 and HL148338). Conception or design of the study, B.K.W. J.O. J.P.C. and R.I.P.; data collection, B.K.W. A.M. J.P.C. A.D. J.G. and O.C.; data analysis and interpretation, B.K.W. A.S. R.A. N.K.R.P. J.O. J.-L.M. and S.K.Y.; drafting the article, B.K.W. J.O. S.K.Y. R.A. J.P.C. and R.I.P. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in their field of research or within their geographical location. We support inclusive, diverse, and equitable conduct of research. Funding Information: Structured illumination microscopy was performed at the Center for Advanced Microscopy, a Nikon Center of Excellence, Department of Integrative Biology & Pharmacology at McGovern Medical School, UTHealth Houston. The authors would like to thank Saurabh Chavan, Xiao Ling, and Emilio Mendiol at Texas A&M University for assisting with the FE simulations; Dr. Manuel Lagache, PhD, from Savoie Mont-Blanc University (Chamb{\'e}ry, France) for help with the FE shear simulations; and Dr. Yohan Payan, PhD, from Laboratory TIMC-CNRS of the University Grenoble-Alpes (Grenoble, France) for helpful discussions. J.O. was funded from February 2020 to September 2020 by Dr. Roderic I. Pettigrew (Welch Chair) on a visiting scholar position at Texas A&M University, Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, USA. This work was supported by a grant from The Welch Foundation . R.A. was partially supported by NIH grant R00HL138288 . This work was additionally supported by grants to J.P.C. ( National Institutes of Health [NIH] R01s HL133254 and HL148338 ). Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = oct,
day = "4",
doi = "10.1016/j.matt.2023.08.010",
language = "English (US)",
volume = "6",
pages = "3608--3630",
journal = "Matter",
issn = "2590-2393",
publisher = "Cell Press",
number = "10",
}