Pattern-Based Contractility Screening, a Reference-Free Alternative to Traction Force Microscopy Methodology

Ghagre, Ajinkya; Amini, Ali; Srivastava, Luv Kishore; Tirgar, Pouria; Khavari, Adele; Koushki, Newsha; Ehrlicher, Allen J.

doi:10.1021/acsami.1c02987

Cited by 15 publications

(14 citation statements)

References 51 publications

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“…The substrate strain energy W S is easily experimentally measured and is often reported as a measure of mechanical activity, see e.g. [11][12][13][14]. The active work done W CA is also clearly important as it can be conceptually linked to the energy that is required to drive the cell into its contractile state, with hard constraints on its possible size [15].…”

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confidence: 99%

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Cell strain energy costs of active control of contractility

Solowiej-Wedderburn¹,

Dunlop²

2022

Preprint

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Cell mechanosensing is implicated in the control of a broad range of cell behaviours, with cytoskeletal contractility a key component. Experimentally, it is observed that the contractility of the cell responds to increasing substrate stiffness, showing increased contractile force and changing the distribution of cytoskeletal elements. Here we show using a theoretical model of active cell contractility that upregulation of contractility need not be energetically expensive, especially when combined with changes in adhesion and contractile distribution. Indeed, we show that a feedback mechanism based on maintenance of strain energy would require an upregulation in contractile pressure on all but the softest substrates. We consider both the commonly reported substrate strain energy and active work done. We demonstrate substrate strain energy would select for the observed clustering of cell adhesions on stiffer substrates which also enable an upregulation of total contractile pressure; while localisation of contractility has the greatest impact on the internal work.

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confidence: 99%

“…Although changes in traction forces are typically measured in mechanostransduction studies, recent work suggests that substrate strain energy can be used as a measure for mechanical activity [11, 12]. It has been suggested that cells may respond to directly changes in substrate strain energy [13].…”

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confidence: 99%

Cell strain energy costs of active control of contractility

Solowiej-Wedderburn¹,

Dunlop²

2022

Preprint

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“…Compliant polydimethylsiloxane (PDMS) substrates of known stiffness were prepared as previously described ( Yoshie et al, 2019 ; Ghagre et al, 2021 ). In brief, parts A and B NuSil 8100 (NuSil Silicone Technologies, United States) were at 1:1 w/w ratios.…”

Section: Methodsmentioning

confidence: 99%

Prostate cancer cells of increasing metastatic potential exhibit diverse contractile forces, cell stiffness, and motility in a microenvironment stiffness-dependent manner

Molter

Muszynski²,

Tao³

et al. 2022

Front. Cell Dev. Biol.

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During metastasis, all cancer types must migrate through crowded multicellular environments. Simultaneously, cancers appear to change their biophysical properties. Indeed, cell softening and increased contractility are emerging as seemingly ubiquitous biomarkers of metastatic progression which may facilitate metastasis. Cell stiffness and contractility are also influenced by the microenvironment. Stiffer matrices resembling the tumor microenvironment cause metastatic cells to contract more strongly, further promoting contractile tumorigenic phenotypes. Prostate cancer (PCa), however, appears to deviate from these common cancer biophysics trends; aggressive metastatic PCa cells appear stiffer, rather than softer, to their lowly metastatic PCa counterparts. Although metastatic PCa cells have been reported to be more contractile than healthy cells, how cell contractility changes with increasing PCa metastatic potential has remained unknown. Here, we characterize the biophysical changes of PCa cells of various metastatic potential as a function of microenvironment stiffness. Using a panel of progressively increasing metastatic potential cell lines (22RV1, LNCaP, DU145, and PC3), we quantified their contractility using traction force microscopy (TFM), and measured their cortical stiffness using optical magnetic twisting cytometry (OMTC) and their motility using time-lapse microscopy. We found that PCa contractility, cell stiffness, and motility do not universally scale with metastatic potential. Rather, PCa cells of various metastatic efficiencies exhibit unique biophysical responses that are differentially influenced by substrate stiffness. Despite this biophysical diversity, this work concludes that mechanical microenvironment is a key determinant in the biophysical response of PCa with variable metastatic potentials. The mechanics-oriented focus and methodology of the study is unique and complementary to conventional biochemical and genetic strategies typically used to understand this disease, and thus may usher in new perspectives and approaches.

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“…DNA force-based sensors can measure precisely the maximal force produced by cells, but not the lower values, and in addition, do not provide information about force directionality (Wang and Ha, 2013). Global or local deformations of micropatterned cells are not precise enough to investigate the finer aspects of how traction force is regulated (Tseng et al, 2011;Pushkarsky et al, 2018;Ghagre et al, 2021). Hence, alternative methods are required to evaluate the relationship between traction force and the biochemical composition of the cytoskeletal network in the same cell.…”

Section: Introductionmentioning

confidence: 99%