Measurement of dynamic cell-induced 3D displacement fields in vitro for traction force optical coherence microscopy

Mulligan, Jeffrey A.; Bordeleau, François; Reinhart‐King, Cynthia A.; Adie, Steven G.

doi:10.1364/boe.8.001152

Cited by 37 publications

(45 citation statements)

References 78 publications

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“…These data show that, at the beginning of each time-lapse experiment, cell force-induced deformations extended further than 100 μm from the cell body. After the addition of the contractility inhibitor (cytochalasin D) 30 minutes into the experiment, there was a delayed onset of cell relaxation, consistent with our prior work using similar force inhibition protocols 15 . Once relaxation began, bead displacements declined until the beads arrived at their reference (i.e., zero deformation) positions at the end of the experiment.…”

Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

“…Motivated by the developing needs of the TFM field and by the limitations of current technologies, we previously proposed a TFM method based upon optical coherence microscopy (OCM) 15 , a variant of optical coherence tomography (OCT) with high transverse resolution. The method, which we named traction force optical coherence microscopy (TF-OCM) 15 , leverages multiple advantages offered by OCM and computed imaging methods to enable the quantitative reconstruction of 3D CTFs with high temporal resolution in scattering media. These advantages include a rapid (minute-scale) volumetric acquisition rate provided by Fourier domain OCM systems, focal plane resolution over an extended depth-of-field achieved with the aid of computational adaptive optics (CAO) 22 , and label-free imaging at near-IR wavelengths to mitigate scattering and photobleaching/phototoxicity concerns.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy

Mulligan

Feng

Adie

2018

Preprint

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11Cellular traction forces (CTFs) play an integral role in both physiological processes and disease, and are a topic of 12 interest in mechanobiology. Traction force microscopy (TFM) is a family of methods used to quantify CTFs in a 13 variety of settings. State-of-the-art 3D TFM methods typically rely on confocal fluorescence microscopy, which can 14 impose limitations on acquisition speed, volumetric coverage, and temporal sampling or coverage. In this report, we 15 present the first quantitative implementation of a new TFM technique: traction force optical coherence microscopy 16(TF-OCM). TF-OCM leverages the capabilities of optical coherence microscopy and computational adaptive optics 17(CAO) to enable the quantitative reconstruction of 3D CTFs in scattering media with minute-scale temporal 18 resolution. We applied TF-OCM to quantify CTFs exerted by isolated NIH-3T3 fibroblasts embedded in Matrigel, 19with five-minute temporal sampling, using images which spanned a 500×500×500 μm 3 field-of-view. Due to the 20 reliance of TF-OCM on computational imaging methods, we have provided extensive discussion of the underlying 21 equations, assumptions, and failure modes of these methods. TF-OCM has the potential to advance studies of 22 biomechanical behavior in scattering media, and may be especially well-suited to the study of cell collectives such 23as spheroids, a prevalent model in mechanobiology research. 24

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Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy

Mulligan

Feng

Adie

2018

Preprint

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“…We expanded our QPOL analysis to complex biological samples, including cell monolayers, ex vivo organoids and tumor tissues to further evaluate the capabilities of our technique. Measuring cellular contractility is difficult in these complex systems and in many cases has not been attempted . In the case of epithelial cell monolayers, which are known to exert contractile forces through their cell–cell junctions , the retardance signal was localized around the cell edge and showed good overlap with the cobblestone architecture of the epithelial monolayer (Figure A ) .…”

Section: Resultsmentioning

confidence: 99%

“…Measuring cellular contractility is difficult in these complex systems and in many cases has not been attempted [8,10,11].…”

Section: Measurement Of Cell Contractility In Complex Biological Samentioning

confidence: 99%

Quantitative assessment of cell contractility using polarized light microscopy

Wang

Miller

Pannullo

et al. 2018

Journal of Biophotonics

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Cell contractility regulates multiple cell behaviors which contribute to both normal and pathological processes. However, measuring cell contractility remains a technical challenge in complex biological samples. The current state of the art technologies employed to measure cell contractility have inherent limitations that greatly limit the experimental conditions under which they can be used. Here, we use quantitative polarization microscopy to extract information about cell contractility. We show that the optical retardance signal measured from the cell body is proportional to cell contractility in 2-dimensional and 3-dimensional platforms, and as such can be used as a straightforward, tractable methodology to assess cell contractility in a variety of systems. This label-free optical method provides a novel and flexible way to assess cellular forces of single cells and monolayers in several cell types, fixed or live, in addition to cells present in situ in mouse tumor tissue samples. This easily implementable and experimentally versatile method will significantly contribute to the cell mechanics field.

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Obesity‐Associated Adipose Stromal Cells Promote Breast Cancer Invasion through Direct Cell Contact and ECM Remodeling

Mulligan

Ouyang

et al. 2020

Adv Funct Materials

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Obesity increases the risk and worsens the prognosis for breast cancer due, in part, to altered adipose stromal cell (ASC) behavior. Whether ASCs from obese individuals increase migration of breast cancer cells relative to their lean counterparts, however, remains unclear. To test this connection, multicellular spheroids composed of MCF10A-derived tumor cell lines of varying malignant potential and lean or obese ASCs are embedded into collagen scaffolds mimicking the elastic moduli of interstitial breast adipose tissue. Confocal image analysis suggests that tumor cells alone migrate insignificantly under these conditions. However, direct cell-cell contact with either lean or obese ASCs enables them to migrate collectively, whereby obese ASCs activate tumor cell migration more effectively than their lean counterparts. Time-resolved optical coherence tomography imaging suggests that obese ASCs facilitate tumor cell migration by mediating contraction of local collagen fibers. Matrix metalloproteinase (MMP)-dependent proteolytic activity significantly contributes to ASC-mediated tumor cell invasion and collagen deformation. However, ASC contractility is also important, as co-inhibition of both MMPs and contractility is necessary to completely abrogate ASC-mediated tumor cell migration. These findings imply that obesity-mediated changes of ASC phenotype may impact tumor cell migration and invasion with potential implications for breast cancer malignancy in obese patients.

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Measurement of dynamic cell-induced 3D displacement fields in vitro for traction force optical coherence microscopy

Cited by 37 publications

References 78 publications

Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy

Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy

Quantitative assessment of cell contractility using polarized light microscopy

Obesity‐Associated Adipose Stromal Cells Promote Breast Cancer Invasion through Direct Cell Contact and ECM Remodeling

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