Inhibition of chromatin condensation disrupts planar cell migration

Forman, Jack; Hine, Briar; Kaonis, Samantha; Ghosh, Soham

doi:10.1080/19491034.2024.2325961

Cited by 2 publications

References 25 publications

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Mechanical Analysis of Cell Migration Using Hybrid Structural Optimization

Havenhill,

Ghosh

2024

Preprint

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Cell migration requires the dynamic formation and dissolution of mechanical structures inside the cytoplasm. Stress fibers are made of F-actin during cell migration driven by the strategic localization of focal adhesion complexes at the cell-substrate interface. The nucleus is also strategically positioned in the cell during the migration and the stress fibers wrap around the nucleus possibly to carry the nucleus with the cell. Cell migration is energetically demanding and should require strategic utilization of resources such as the F-actin stress fiber formation at specific locations so that they generate enough force by actomyosin contraction at the cell-matrix adhesion sites for a directed movement. In this work we propose a structural optimization based biophysical model to predict the strategic localization and sizes of F-actin fibers that supports the nucleus and the cytoplasm during migration. With the use of a nonlinear controller via a Newton-Euler-based model of the generated design, we further quantified the force in the stress fibers during migration, with results close to those obtained through experimental methods such as traction force microscopy. The predicted force decreases for a cell that migrates slowly due to a pharmacological perturbation. Such quantification of forces only require the information of the trajectory of the cell that can be readily obtained from time lapse microscopy. With novel microscopy techniques emerging, such biophysical model framework can be combined with traction force microscopy data to achieve unprecedented mechanical information inside and outside cells during migration, which is otherwise not possible by experiments only.

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Mechanical Analysis of Cell Migration Using Hybrid Structural Optimization

Havenhill,

Ghosh

2024

Preprint

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Mechanically Induced Deformation of Nuclei in the Tricuspid Valve Interstitial Cells: Experimental Measurements and Multi-scale Computational Simulation

Pakzadmanesh,

Salinas,

Thomas

et al. 2024

ASME Open Journal of Engineering

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We examined the mechanical deformation of valve interstitial cells (VICs) in the anterior leaflet of the tricuspid valve and explored the relationship between the extracellular matrix (ECM) structure and cellular mechanics. Fresh porcine hearts were used to prepare specimens, subjected to biaxial tensile testing, and imaged using confocal microscopy with VIC nuclei staining. A multi-scale computational framework was developed to analyze cellular deformation and orientation within the ECM, using nuclear aspect ratio (NAR) as a metric. Experimental results showed that NAR values increased with mechanical loading, from 2.57±0.72 in a traction-free state to 3.4±1.29 at 130 kPa. Model predictions aligned with experimental findings. They also highlighted the significant impact of ECM fiber orientation on VIC nuclei deformation. These results indicate that mechanical forces profoundly influence cellular morphology and, potentially, their function. Further development of models is necessary to understand the complex interplay between the mechanical environment and cellular responses, crucial for identifying how mechanical forces affect tricuspid valve function and malfunction.

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Inhibition of chromatin condensation disrupts planar cell migration

Cited by 2 publications

References 25 publications

Mechanical Analysis of Cell Migration Using Hybrid Structural Optimization

Mechanical Analysis of Cell Migration Using Hybrid Structural Optimization

Mechanically Induced Deformation of Nuclei in the Tricuspid Valve Interstitial Cells: Experimental Measurements and Multi-scale Computational Simulation

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