Cell engineering: Biophysical regulation of the nucleus

Song, Yang; Soto, Jennifer; Bin-ru, Chen; Yang, Li; Li, Song

doi:10.1016/j.biomaterials.2019.119743

Cited by 42 publications

(32 citation statements)

References 314 publications

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“…Similarly, Downing et al, by means of linear topographies, studied the epigenetic pathways linked to somatic cell reprogramming toward pluripotent stem cell lineage. Here, it has been shown that by tuning topography structural features, it is possible to obtain the same epigenetic modifications (i.e., histones modifications) normally induced through chemical stimulation (Song et al, 2020). Nuclear shape and mechanics could also be altered with micro pillar-based topographies.…”

Section: Topographiesmentioning

confidence: 99%

“…This represents a multidisciplinary field, which combines cuttingedge technologies in complementary research areas, such as materials science, cell and molecular biology, and advanced imaging. The use of engineered materials and platforms provides unparalleled opportunities of mechanical stimulation by modulating cellular tensional state (Song et al, 2020). Here, micro-and nano-fabrication techniques, chemical patterning, and material chemistry allow in fact the finetuning of cell/substrate interaction.…”

Section: Introductionmentioning

confidence: 99%

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Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

Pennacchio

Nastały

Poli

et al. 2021

Front. Bioeng. Biotechnol.

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Cells sense a variety of different mechanochemical stimuli and promptly react to such signals by reshaping their morphology and adapting their structural organization and tensional state. Cell reactions to mechanical stimuli arising from the local microenvironment, mechanotransduction, play a crucial role in many cellular functions in both physiological and pathological conditions. To decipher this complex process, several studies have been undertaken to develop engineered materials and devices as tools to properly control cell mechanical state and evaluate cellular responses. Recent reports highlight how the nucleus serves as an important mechanosensor organelle and governs cell mechanoresponse. In this review, we will introduce the basic mechanisms linking cytoskeleton organization to the nucleus and how this reacts to mechanical properties of the cell microenvironment. We will also discuss how perturbations of nucleus–cytoskeleton connections, affecting mechanotransduction, influence health and disease. Moreover, we will present some of the main technological tools used to characterize and perturb the nuclear mechanical state.

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Section: Topographiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

Pennacchio

Nastały

Poli

et al. 2021

Front. Bioeng. Biotechnol.

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“…The morphology and deformation of cellular nuclei influences differentiation, immune response, migration and disease development (1). Regarding migration, many cancer and immune cells have highly deformable nucleus (2)(3)(4)(5), increasing their migratory potential by enabling passage through narrow matrix pores.…”

Section: Introductionmentioning

confidence: 99%

Investigation of cell nucleus heterogeneity

Reynolds

McEvoy

Ghosh

et al. 2020

Preprint

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AbstractNucleus deformation has been shown to play a key role in cell mechanotransduction and migration. Therefore, it is of wide interest to accurately characterize nucleus mechanical behavior. In this study we present the first computational investigation of the in-situ deformation of a heterogeneous cell nucleus. A novel methodology is developed to accurately reconstruct a three-dimensional finite element spatially heterogeneous model of a cell nucleus from confocal microscopy z-stack images of nuclei stained for nucleus DNA. The relationship between spatially heterogeneous distributions microscopic imaging-derived greyscale values, shear stiffness and resultant shear strain is explored through the incorporation of the reconstructed heterogeneous nucleus into a model of a chondrocyte embedded in a PCM and cartilage ECM. Externally applied shear deformation of the ECM is simulated and computed intra-nuclear strain distributions are directly compared to corresponding experimentally measured distributions. Simulations suggest that the nucleus is highly heterogeneous in terms of its mechanical behaviour, with a sigmoidal relationship between experimentally measure greyscale values and corresponding local shear moduli (μn). Three distinct phases are identified within the nucleus: a low stiffness phase (0.17 kPa ≤ μn ≤ 0.63 kPa) corresponding to mRNA rich interchromatin regions; an intermediate stiffness phase (1.48 kPa ≤ μn ≤ 2.7 kPa) corresponding to euchromatin; a high stiffness phase (3.58 kPa ≤ μn ≤ 4.0 kPa) corresponding to heterochromatin. Our simulations indicate that disruption of the nucleus envelope associated with lamin-A/C depletion significantly increases nucleus strain in regions of low DNA concentration. A phenotypic shift of chondrocytes to fibroblast-like cells, a signature for osteoarthritic cartilage, results in a 35% increase in peak nucleus strain compared to control. The findings of this study may have broad implications for the current understanding of the role of nucleus deformation in cell mechanotransduction.

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“…The substrate resistance experienced consequently allows the cell to mechanically sense its environment although the details of the physical mechanism of August 6, 2020 3/30 this signal transduction remains unclear. FAs have received most attention as mechanosensors [32][33][34], although there is an increasing awareness of the need to account for mechanosensing across the cell including at the nuclear envelope [35,36].…”

Section: Introductionmentioning

confidence: 99%

Sticking around: Optimal cell adhesion patterning for energy minimization and substrate mechanosensing

Solowiej-Wedderburn¹,

Dunlop

2020

Preprint

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Cell mechanotransduction, in which cells sense and respond to the physical properties of their micro-environments, is proving fundamental to understanding cellular behaviours across biology. Tissue stiffness (Young’s modulus) is typically regarded as the key control parameter and bioengineered gels with defined mechanical properties have become an essential part of the toolkit for interrogating mechanotransduction. We here, however, show using a mechanical cell model that the effective substrate stiffness experienced by a cell depends not just on the engineered mechanical properties of the substrate but critically also on the particular arrangement of adhesions between cell and substrate. In particular, we find that cells with different adhesion patterns can experience two different gel stiffnesses as equivalent and will generate the same mean cell deformations. For small adhesive patches, which mimic experimentally observed focal adhesions, we demonstrate that the observed dynamics of adhesion growth and elongation can be explained by energy considerations. Significantly we show different focal adhesions dynamics for soft and stiff substrates with focal adhesion growth not preferred on soft substrates consistent with reported dynamics. Equally, fewer and larger adhesions are predicted to be preferred over more and smaller, an effect enhanced by random spot placing with the simulations predicting qualitatively realistic cell shapes in this case. The model is based on a continuum elasticity description of the cell and substrate system, with an active stress component capturing cellular contractility. This work demonstrates the necessity of considering the whole cell-substrate system, including the patterning of adhesion, when investigating cell stiffness sensing, with implications for mechanotransductive control in biophysics and tissue engineering.

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Cell engineering: Biophysical regulation of the nucleus

Cited by 42 publications

References 314 publications

Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

Tailoring Cellular Function: The Contribution of the Nucleus in Mechanotransduction

Investigation of cell nucleus heterogeneity

Sticking around: Optimal cell adhesion patterning for energy minimization and substrate mechanosensing

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