Cell nucleus elastography with the adjoint-based inverse solver

Mei, Yue; Feng, Xuan; Jin, Yun; Kang, Rongyao; Wang, XinYu; Zhao, Dongmei; Ghosh, Soham; Neu, Corey P.; Avril, Stephane

doi:10.1016/j.cmpb.2023.107827

Cited by 6 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The central problem is how to determine the sample mechanical properties, given the sample displacement and boundary conditions. This is known as the inverse problem [20,40,41], for which solutions have been presented in ultrasound elastography [42]. In OCE, Dong et.…”

Section: Introductionmentioning

confidence: 99%

Tumor spheroid elasticity estimation using mechano-microscopy combined with a conditional generative adversarial network

Foo,

Shaddy,

Murgoitio-Esandi

et al. 2024

Preprint

View full text Add to dashboard Cite

Techniques for imaging the mechanical properties of cells are needed to study how cell mechanics influence cell function and disease progression. Mechano-microscopy (a high-resolution variant of compression optical coherence elastography) generates elasticity images of a sample undergoing compression from the phase difference between optical coherence microscopy (OCM) B-scans. However, the existing mechano-microscopy signal processing chain (referred to as the algebraic method) assumes the sample stress is uniaxial and axially uniform, such that violation of these assumptions reduces the accuracy and precision of elasticity images. Furthermore, it does not account for prior information regarding the sample geometry or mechanical property distribution. In this study, we investigate the feasibility of training a conditional generative adversarial network (cGAN) to generate elasticity images from phase difference images of samples containing a cell spheroid embedded in a hydrogel. To train and test the cGAN, we constructed 30,000 elasticity and phase difference image pairs, where elasticity images were generated using a parametric model to simulate artificial samples, and phase difference images were computed using finite element analysis to simulate compression applied to the artificial samples. By applying both the cGAN and algebraic methods to simulated phase difference images, our results indicate the cGAN elasticity images exhibit better spatial resolution and sensitivity. We also evaluated the cGAN on experimental phase difference images of real spheroids embedded in hydrogels and compared the cGAN elasticity with the algebraic elasticity, OCM, and confocal fluorescence microscopy, and found the cGAN elasticity is often more robust to noise, especially within stiff nuclei.

show abstract

Section: Introductionmentioning

confidence: 99%

Tumor spheroid elasticity estimation using mechano-microscopy combined with a conditional generative adversarial network

Foo,

Shaddy,

Murgoitio-Esandi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In previous studies, bulk nuclear mechanics and shape were considered while understanding the nuclear role of cell migration; however, the role of chromatin-level mechanics and its dynamic nature in cell migration has not been investigated so far although previous studies indicate the possibility of the requirement of chromatin compaction during cell migration [ 8 ]. Some investigations have shown that intranuclear mechanics can be spatially variable [ 9–11 ], which has implications for how mechanical force is experienced by the cell nucleus. Because cells experience heterogeneous levels of cytoskeletal forces at different cell locations, it is possible that different locations inside the nucleus experience different amounts of force and chromatin movement to coordinate local nuclear mechanics with local cell mechanics, as shown in chondrocyte deformation during osmotic loading [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of chromatin condensation disrupts planar cell migration

Forman,

Hine,

Kaonis

et al. 2024

Nucleus

Self Cite

View full text Add to dashboard Cite

Cell migration involves the actin cytoskeleton, and recently recognized nuclear involvement. In this study, we explore the impact of chromatin remodeling on cell migration using NIH 3T3 cells and a scratch wound assay subjected to pharmacological interventions. We inhibit histone deacetylases (HDACs) with Trichostatin A (TSA) and methyltransferase EZH2 with GSK126 to modulate chromatin compaction. Our results indicate that chromatin modifications impair wound closure efficiency, reduce individual cell migration speed, and disrupt migration persistence. Live-cell imaging reveals dynamic intranuclear chromatin remodeling and nuclear shape parameters during migration, influenced by both small- and large-scale chromatin remodeling. The altered nuclear shape is associated with disrupted cell and nuclear mechanics, suggesting a crucial interplay between chromatin remodeling, nuclear mechanics and migration. These findings shed light on the intricate connection between intranuclear chromatin dynamics, nuclear mechanics, and cell migration, providing a basis for further investigations into the molecular mechanisms governing these processes.

show abstract

“…Newly discovered studies point towards the emerging roles of intranuclear chromatin level heterogeneity in cell functions (8). Accordingly, some investigations have shown that intranuclear mechanics can be spatially variable (9)(10)(11), which has implications for how mechanical force is experienced by the cell nucleus. Because cells experience heterogeneous levels of cytoskeletal forces at different cell locations, it is possible that different locations inside the nucleus experience different amounts of force and chromatin movement to coordinate local nuclear mechanics with local cell mechanics, as shown in chondrocyte deformation during osmotic loading (12).…”

Section: Introductionmentioning

confidence: 99%

Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration

Forman,

Hine,

Kaonis

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

The cell nucleus plays a critical role in cell migration by its deformability under forces, by acting as a piston that activates mechanosensitive channels, and also by serving as a ruler tailoring cell response to spatial constraints. Cell nuclear mechanics determine the mechanobiology of static and migrating cells. Here, we report that intranuclear chromatin architecture plays a previously unknown role during cell migration on planar substrates. By inhibiting histone deacetylation, which compacts chromatin, and a methyltransferase, which affects chromatin remodeling and chromatin compaction, we showed that cell migration speed and persistence drastically slowed wound closure efficiency in an in vitro scratch wound assay. Chromatin remodeling was visualized and quantified during cell migration, which may be intertwined with nuclear mechanics and shape. Inhibition disrupts remodeling and other unknown roles in chromatin, thus affecting the speed and persistence of cell migration. Interestingly, cytoskeletal stress fiber formation and cell shape were not visibly affected by chromatin modifications, suggesting an exclusive nuclear mechanobiological role in cell migration. These findings provide new insights into how aging and other degenerative conditions affect the plasticity of chromatin architecture and hence its effect on cell migration efficiency.

show abstract

Cell nucleus elastography with the adjoint-based inverse solver

Cited by 6 publications

References 44 publications

Tumor spheroid elasticity estimation using mechano-microscopy combined with a conditional generative adversarial network

Tumor spheroid elasticity estimation using mechano-microscopy combined with a conditional generative adversarial network

Inhibition of chromatin condensation disrupts planar cell migration

Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration

Contact Info

Product

Resources

About