Proliferation of Cells with Severe Nuclear Deformation on a Micropillar Array

Liu, Ruili; Yao, Xiang; Liu, Xiangnan; Ding, Jiandong

doi:10.1021/acs.langmuir.8b03452

Cited by 26 publications

(25 citation statements)

References 111 publications

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“…7b) leading to an important reduction of the distance between the nuclear lamina and the micropillar boundary. Additionally, the nucleus starts acquiring a 'peanut' shape as it has been experimentally observed for different cellular phenotypes including mesenchymal stem cells, osteosarcoma cells and bone marrow stroma cells [11][12][13][14]. Such an outcome becomes even more evident when the nuclear lamina is ablated (S 3 ) (Fig.…”

Section: Comparison With Experimental Datamentioning

confidence: 65%

“…To do so, patterned microfluidic devices have been employed during the last few years in order to characterize the cell mechanical behaviour [8,9] and the nucleus self-deformations [10][11][12][13] and shape changes [14,15] induced by mechanical forces, which are due to the interaction between the cell and the topological surface. Assays on micropillared substrates involve successive steps: (i) contact between the cell and the pillars, (ii) adhesion of the cell on the pillars surface, (iii) cell spreading, (iv) cell polarization and (v) cell crawling.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Stress-Strain State over Micropillars: A Mechanical In silico Study

Allena¹,

Aubry²

2022

Molecular &Amp; Cellular Biomechanics

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Cells adapt to their environment and stimuli of different origin. During confined migration through sub-cellular and sub-nuclear pores, they can undergo large strains and the nucleus, the most voluminous and the stiffest organelle, plays a critical role. Recently, patterned microfluidic devices have been employed to analyze the cell mechanical behavior and the nucleus self-deformations. In this paper, we present an in silico model to simulate the interactions between the cell and the underneath microstructured substrate under the effect of the sole gravity. The model lays on mechanical features only and it has the potential to assess the contribution of the nuclear mechanics on the cell global behavior. The cell is constituted by the membrane, the cytosol, the lamina, and the nucleoplasm. Each organelle is described through a constitutive law defined by specific mechanical parameters, and it is composed of a fluid and a solid phase leading to a viscoelastic behavior. Our main objective is to evaluate the influence of such mechanical components on the nucleus behavior. We have quantified the stress and strain distributions in the nucleus, which could be responsible of specific phenomena such as the lamina rupture or the expression of stretch-sensitive proteins.

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Section: Comparison With Experimental Datamentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Nuclear Stress-Strain State over Micropillars: A Mechanical In silico Study

Allena¹,

Aubry²

2022

Molecular &Amp; Cellular Biomechanics

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“…In fact, according to the experimental data presented in Erk et al (2010) and Storm et al (2005), the Young modulus of the actin fibres exponentially increases as a function of the strain. If this was the case here, the raising of the stiffening phenomenon would inhibit the cell penetration in between the pillars and we would not obtain the nucleus self-deformation as it has been experimentally observed (Morgan et al 2007;Geiger et al 2009;Liu et al 2017Liu et al , 2018. Thus, as explained in Sect.…”

Section: Nucleus and Cytoplasm Deformation On Micropillared Substratementioning

confidence: 75%

“…Micropillars are most commonly employed as an array of thin beams in traction force microscopy to access the interaction forces between a cell and its substrate (Tan et al 2003;du Roure et al 2005;Ghibaudo et al 2011). Additionally, by controlling the material used, the size of the pillars and the gap size between pillars, they can serve to control the shape of the nucleus (Pan et al 2012;Hanson et al 2015) and investigate the process of nuclear self-deformation induced by mechanical forces generated by the topological surface (Davidson et al 2010;Badique et al 2013;Liu et al 2017Liu et al , 2018. These recent experiments offer a new insight on nuclear deformation and raise further questions: is gravity driving this movement (Pan et al 2012)?…”

Section: Introductionmentioning

confidence: 99%

“…Once the cell has touched the underneath substrate, it starts developing the FAs to create a mechanical link between the intra-cellular actin filaments and the substrate surface (Abercrombie et al 1970). Then, FAs play the role of anchoring points that restrain cell contraction while promoting cell protrusion at the leading edge and nucleus self-deformation through the pillars (Morgan et al 2007;Geiger et al 2009;Liu et al 2017Liu et al , 2018. It has been observed that the nucleus may undergo large and severe deformations as a function of the cellular phenotype and the nuclear size.…”

Section: Introductionmentioning

confidence: 99%

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In silico approach to quantify nucleus self-deformation on micropillared substrates

Mondésert-Deveraux

Aubry

Allena

2019

Biomech Model Mechanobiol

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Considering the major role of confined cell migration in biological processes and diseases, such as embryogenesis or metastatic cancer, it has become increasingly important to design relevant experimental setups for in vitro studies. Microfluidic devices have recently presented great opportunities in their respect since they offer the possibility to study all the steps from a suspended to a spread, and eventually crawling cell or a cell with highly deformed nucleus. Here, we focus on the nucleus self-deformation over a micropillared substrate. Actin networks have been observed at two locations in this setup: above the nucleus, forming the perinuclear actin cap (PAC), and below the nucleus, surrounding the pillars. We can then wonder which of these contractile networks is responsible for nuclear deformation. The cytoplasm and the nucleus are represented through the superposition of a viscous and a hyperelastic material and follow a series of processes. First, the suspended cell settles on the pillars due to gravity. Second, an adhesive spreading force comes into play, and then, active deformations contract one or both actin domains and consequently the nucleus. Our model is first tested on a flat substrate to validate its global behaviour before being confronted to a micropillared substrate. Overall, the nucleus appears to be mostly pulled towards the pillars, while the mechanical action of the PAC is weak. Eventually, we test the influence of gravity and prove that the gravitational force does not play a role in the final deformation of the nucleus.

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Generation of Human iPSC‐Derived Neurons on Nanowire Arrays Featuring Varying Lengths, Pitches, and Diameters

Harberts

Siegmund

Hedrich

et al. 2022

Adv Materials Inter

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In this context, vertically aligned high aspect ratio nanostructures-so-called nanowire (NW) arrays-used as cell culture substrates play an increasingly important role in establishing novel tools for interrogating and stimulating cells on molecular and cellular levels. [4][5][6][7] In recent years, studies testing the unique capabilities of NW arrays have been conducted with a variety of cell types, for instance, basic cell lines such as GPE86, HEK293, and HeLa cells, primary rodent neurons, and (mesenchymal) stem cells (MSCs), to name a few. [8,9] The impact of such studies on medical applications such as drug screenings and neurodegenerative disease studies might, however, be significantly improved by employing more sophisticated cells, namely, cells derived from human induced pluripotent stem cells (iPSCs). [10] Human iPSC technologies have changed the way of preclinical research and application by enabling human (patientspecific) in vitro models without restrictions in cell availability. [11] Not only political and ethical controversies raised by using embryonic stem cells (ESCs) are avoided, but also all major cell types including blood-brain barrier models and brain organoids can be generated. [12,13] For studying neurodegenerative diseases such as Alzheimer's or Parkinson's, neurons derived from human iPSCs are of particular interest since adequate models are otherwise scarcely available. [14] Apart from ESCs,

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Proliferation of Cells with Severe Nuclear Deformation on a Micropillar Array

Cited by 26 publications

References 111 publications

Nuclear Stress-Strain State over Micropillars: A Mechanical In silico Study

Nuclear Stress-Strain State over Micropillars: A Mechanical In silico Study

In silico approach to quantify nucleus self-deformation on micropillared substrates

Generation of Human iPSC‐Derived Neurons on Nanowire Arrays Featuring Varying Lengths, Pitches, and Diameters

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