Quantifying the Traction Force of a Single Cell by Aligned Silicon Nanowire Array

Li, Zhou; Song, Jinhui; Mantini, G.; Lu, Ming; Fang, Hao; Falconi, Christian; Chen, Lih‐Juann; Wang, Zhong Lin

doi:10.1021/nl901774m

Cited by 117 publications

(122 citation statements)

References 44 publications

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“…2D and S5). In contrast, bulk traction forces normally vary among different cell lines (20)(21)(22). Our observation suggests that there exists a common tension threshold value for the molecular tension generated by cells on an active integrin α V β 3 during adhesion.…”

mentioning

confidence: 71%

Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling

Wang

2013

Science

494

657

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Cell-cell and cell-matrix mechanical interactions through membrane receptors direct a wide range of cellular functions and orchestrate the development of multicellular organisms. To define the single molecular forces required to activate signaling through a ligand-receptor bond, we developed the Tension Gauge Tether (TGT) approach in which the ligand is immobilized to a surface through a rupturable tether before receptor engagement. TGT serves as an autonomous gauge to restrict the receptor-ligand tension. Using a range of tethers with tunable tension tolerances, we show that cells apply a universal peak tension of ~40 pN to single integrin-ligand bonds during initial adhesion. We find that less than 12 pN is required to activate Notch receptors. TGT can also provide a defined molecular mechanical cue to regulate cellular functions.Cells sense and respond to the mechanical properties of the surrounding extracellular matrix (ECM) and neighboring cells. Reciprocally, cells also apply force on the ECM and transmit mechanical signals to neighboring cells. These mechanical interactions activate intracellular signaling pathways and regulate such diverse processes as cell adhesion, polarization, migration, proliferation and differentiation (1, 2). As a result, by tuning bulk mechanical properties like stiffness, texture, and geometry of the substrate, researchers have gained insight into processes such as stem cell differentiation (3) and tumor metastasis (4). Singlemolecule force spectroscopy has been used to study various mechano-sensitive membrane receptors including integrin, cadherin and Notch (5-8). However, these approaches cannot reveal the single molecule forces required for physiological functions because they either measure collective forces exerted through many molecules or probe molecular unbinding or unfolding forces only. More recently, FRET-based force sensors were developed and inserted to target sites to monitor cellular forces (9, 10), but great efforts must be taken to prepare the sensors and to track and interpret the fluorescence signal. Here, we describe a platform termed Tension Gauge Tether (TGT) that allows us to determine the single molecule forces required for mechanical signaling in cells.In TGT, a ligand is covalently conjugated to a tether that ruptures at a critical force, which we term `tension tolerance' or T tol , and is immobilized on a solid surface through the tether (Fig. 1). Cells are plated on the surface and membrane receptors engage with and apply tension to the ligands. If signal activation through the receptor requires a molecular tension larger than T tol , the tether will rupture, abolishing signal activation. In contrast, if the required tension is smaller than T tol , the tether will endure, activating the receptor-mediated signaling. By engineering a series of tethers with different T tol values, the tension required for signal activation can be determined by observing receptor-regulated cell activities which * To whom correspondence should be addressed. tjha@il...

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confidence: 71%

Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling

Wang

2013

Science

494

657

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“…37 To investigate the force-displacement relationship of SiNWs with differing diameter, we measured lateral force by atomic force microscopy in contact mode, during which a constant force between the tip and SiNWs is applied, as shown in Figure 4a. 38 To deflect a SiNW with (Figure 4g).…”

Section: Resultsmentioning

confidence: 99%

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

et al. 2016

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Cellular adhesion and growth on substrates with differing surface topography are known to induce unusual cell behaviors. Here, we investigated the adhesion and growth of human embryonic kidney 293T cells on vertically aligned silicon nanowires. Varying the diameter of nanowires affected their elasticity, which in turn caused variations in cell morphology and adhesion. Calculation of their elastic modulus revealed that long and thin nanowires are easier to deflect and thus provide more focal adhesion sites for adherent cells. And, induced mechanical tension triggered cellular anisotropic growth in the direction of tension, creating a greater rate of filopodium growth than was observed with a bare glass substrate devoid of mechanical tension. This nanotopographical approach provides important insights into the role of artificial substrates in the modulation of cell behavior and a conceptual framework for further analysis of substrate-induced changes in cellular activity.

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“…Cancer cells invading other tissues form actin rich structures called invadopodia. 20 High protrusive forces are essential in order for cancer cells to metastasize and invade other tissues, 6 and future work will examine and quantify these forces in cancer cells. The technology presented here can potentially be useful for cancer diagnosis and in furthering understanding of the fundamental biological problems.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a change in the force a cell exerts on a surface could be an indication of disease; it has been reported that cancer cells exhibit a larger force than normal cells, by $ 20% to 50%. 6 Recent advances in microfabrication have enabled direct observation and quantitative analysis at the single cell level, thus providing accurate information that is helpful in explaining how cells function.…”

Section: Introductionmentioning

confidence: 99%

New approach for measuring protrusive forces in cells

Mathur¹,

Roca‐Cusachs²,

Rossier³

et al. 2011

Journal of Vacuum Science & Technology B, Nanotechnology an

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Quantifying the Traction Force of a Single Cell by Aligned Silicon Nanowire Array

Abstract: ABSTRACT

Cited by 117 publications

References 44 publications

Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling

Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

New approach for measuring protrusive forces in cells

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