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Experimental and Computational Elucidation of Mechanical Forces on Cell Nucleus

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1 Department of Mechanical and Aerospace Engineering, University of Florida (UF), Gainesville, FL, 32611, USA
2 Department of Chemical Biology & Medicinal Chemistry, University of Texas at Austin, TX, 78712, USA
3 UF Health Cancer Center (UFHCC), Gainesville, FL, 32611, USA
4 Department of Mechanical Engineering, Northwestern University, Evanston, IL, 60208, USA
5 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22901, USA

* Corresponding Author: Xin Tang. Email:

The International Conference on Computational & Experimental Engineering and Sciences 2024, 32(1), 1-2. https://doi.org/10.32604/icces.2024.011130

Abstract

Mechanotransduction, i.e., living cells sense and transduce mechanical forces into intracellular biochemical signaling and gene expression, is ubiquitous across diverse organisms. Increasing evidence suggests that mechanotransduction significantly influences cell functions and its mis-regulation is at the heart of various pathologies. A quantitative characterization of the relationship between mechanical forces and resulted mechanotransduction is pivotal in understanding the rules of life and innovating new therapeutic strategies [1-3]. However, while such relationship on the cell surface membrane and cytoskeleton have been well studied, little is known about whether/how mechanical forces applied on the cell interior nucleus (“headquarter of the cell”) quantitatively trigger mechanotransduction [4-5]. This is because conventional techniques cannot simultaneously access, manipulate, and record the mechano-chemo-genetic dynamics inside the cell nucleus. In this presentation, we will present our new results on (1) the experimental characterization of the translocation of YAP (Yes-associated protein) induced by quantitative force applied directly on the nucleus; and (2) computation-guided quantification of applied mechanical forces [6-7]. Our results suggest that magnetic microbeads can regulate the dynamic YAP translocation and downstream gene transcription while avoiding the interruption of cytoskeleton and corresponding important cell functions. Our experimental and computational results advance the understanding of the mechanisms of nuclear mechanotransduction and potentially contribute to the development of new therapies for tumor suppression targeting YAP.

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