Diffuse and nonlinear imaging of multiscale vascular parameters for in vivo monitoring of preclinical mammary tumors

Karrobi, Kavon; Tank, Anup; Tabassum, Syeda; Pera, Vivian; Roblyer, Darren

doi:10.1002/jbio.201800379

Cited by 10 publications

(5 citation statements)

References 56 publications

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“…Using differential interference contrast (DIC) microscopy, these macro-spheroids were imaged continuously as constituent cells proliferated, remodeled the matrix, and initiated invasion. We then used optical clearing ( Susaki et al., 2015 ) and multiphoton microscopy ( Karrobi et al., 2019 ) to obtain stacked images of DAPI-stained nuclei and used second harmonic generation (SHG) signal to obtain images of surrounding collagen ( Figures 2 A and 2B). Within the macro-spheroid, cell-free voids were frequently observed due to the presence of Matrigel ( Figure S6 ).…”

Section: Resultsmentioning

confidence: 99%

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

et al. 2021

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Summary It is well established that the early malignant tumor invades surrounding extracellular matrix (ECM) in a manner that depends upon material properties of constituent cells, surrounding ECM, and their interactions. Recent studies have established the capacity of the invading tumor spheroids to evolve into coexistent solid-like, fluid-like, and gas-like phases. Using breast cancer cell lines invading into engineered ECM, here we show that the spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front. Using a computational approach, we further show that these patterns are captured by a novel jamming phase diagram. We suggest that non-equilibrium phase separation based upon jamming and unjamming transitions may provide a unifying physical picture to describe cellular migratory dynamics within, and invasion from, a tumor.

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Section: Resultsmentioning

confidence: 99%

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

et al. 2021

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“…Imaging of collagen in the bovine lung samples was accomplished through SHG imaging with an upright Multiphoton Microscopy (MPM) system (Ultima Investigator, Bruker, Billerica, MA, USA) [62]. Details of the MPM system are described in detail elsewhere [63]. Briefly, the MPM system consisted of a femtosecond laser source (Spectra Physics, Insight DS+, Santa Clara, CA, USA) tuned to 1050 nm, which provided the excitation for SHG imaging.…”

Section: Engineering Stressmentioning

confidence: 99%

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Jawde

Karrobi

Roblyer

et al. 2021

J. R. Soc. Interface.

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Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure–volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure–volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.

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“…Using differential interference contrast (DIC) microscopy, these macro-spheroids were imaged continuously as constituent cells proliferated, remodeled the matrix, and initiated invasion. We then used optical clearing (28) and multiphoton microscopy (29) to obtain stacked images of DAPI-stained nuclei and used second harmonic generation (SHG) signal to obtain images of surrounding collagen ( Fig. 2A-B).…”

Section: In the Mcf-10a Macro-spheroid The Periphery Invades As A Lomentioning

confidence: 99%

Tumor invasion as non-equilibrium phase separation

Kang

Ferruzzi²,

Spatarelu

et al. 2020

Preprint

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TWO-SENTENCE SUMMARY: Using a multicellular spheroid embedded within an engineered threedimensional matrix, we show here the potential for coexistence of solid-like, fluid-like, and gas-like phases of the cellular collective described by a jamming phase diagram. Depending upon cell type and matrix density, moreover, invasion into matrix from the tumor periphery can switch from a continuous cellular collective that flows like a fluid to discrete cells that scatter individually like a gas. ASTRACT:The early malignant tumor invades surrounding extracellular matrix (ECM) in a manner that depends upon material properties of constituent cells and ECM. Biophysical mechanisms remain unclear, however. Using a multicellular spheroid embedded within an engineered three-dimensional matrix, we show here the potential for coexistence of solid-like, fluid-like, and gas-like phases of the cellular collective described by a jamming phase diagram. Depending upon cell type (MCF-10A vs. MDA-MB-231) and ECM density (1 to 4 mg/ml collagen), cancer cells within the spheroid display a variety of collective behaviors, including a nonmigratory jammed phase and a migratory unjammed phase. At a critical collagen density, unjammed cancer cells at the spheroid periphery transition in an almost switch-like fashion between distinct modes of invasion. In the case of MDA-MB-231, for example, we find that when ECM density is 2 mg/ml or smaller single cells and cell clusters scatter from the spheroid periphery in the form of discrete gas-like particles, but when ECM density is 3 mg/ml or greater these cells flow collectively from the spheroid periphery in continuous fluid-like invasive branches. These findings suggest coexistence within the spheroid mass of multiple material phases of the cellular collective -solid-like, fluid-like, and gas-like-in a manner that is superficially similar to common inanimate multiphasic systems at thermodynamic equilibrium, but here arising in living cellular systems, all of which are displaced far from thermodynamic equilibrium. We conclude that non-equilibrium phase separation based upon jamming dynamics may provide a new physical picture to describe cellular migratory dynamics within and invasion from a tumor mass.Quantum Photonics. D.R. acknowledges the Department of Defense (DoD grant W81XWH-15-1-0070). We also gratefully acknowledge Elizabeth Bartolak-Suki (Boston University) for expert assistance with spheroid histology, and Lauren O'Keeffe (Cornell University) for assistance with spheroid embedding and cell counting. METHODSCell lines and culture media. Non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines were purchased from American Type Cell Culture Collection (ATCC) and cultured using standardized media and conditions [21,52]. MCF-10A cells were cultured in DMEM/F-12 (ThermoFisher, No. 11330032) supplemented with 5% horse serum (Invitrogen, No. 16050122), 20 ng/ml EGF (Peprotech, AF10015; ThermoFisher, No. 10605HNAE), 0.5 mg/ml hydrocortisone (Sigma-Aldrich, No. H0888), 100 ng/ml ...

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Diffuse and nonlinear imaging of multiscale vascular parameters for in vivo monitoring of preclinical mammary tumors

Cited by 10 publications

References 56 publications

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

A novel jamming phase diagram links tumor invasion to non-equilibrium phase separation

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Tumor invasion as non-equilibrium phase separation

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