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Abstract Embedding a collective of tumor cells, i.e. a tumor spheroid, in a fibrous environment, such as a collagen network, provides an essentialin vitroplatform to investigate the biophysical mechanisms of tumor invasion. To predict new mechanisms, we develop a three-dimensional computational model of an embedded spheroid using a vertex model, with cells represented as deformable polyhedrons, mechanically coupled to a fiber network via active linker springs. As the linker springs actively contract, the fiber network remodels. As we tune the rheology of the spheroid and the fiber network stiffness, we find that both factors affect the remodeling of the fiber network with fluid-like spheroids densifying and radially realigning the fiber network more on average than solid-like spheroids but only for a range of intermediate fiber network stiffnesses. Our predictions are supported by experimental studies comparing non-tumorigenic MCF10A spheroids and malignant MDA-MB-231 spheroids embedded in collagen networks. The spheroid rheology-dependent effects are the result of cellular motility generating spheroid shape fluctuations. These shape fluctuations lead to emergent feedback between the spheroid and the fiber network to further remodel the fiber network. This emergent feedback occurs only at intermediate fiber network stiffness since at low fiber network stiffness, the mechanical response of the coupled system is dominated by the spheroid and for high fiber network stiffness, the mechanical response is dominated by the fiber network. We are therefore able to quantify the regime of optimal spheroid-fiber network mechanical reciprocity. Our results uncover intricate morphological-mechanical interplay between an embedded spheroid and its surrounding fiber network with both spheroid contractile strengthandspheroid shape fluctuations playing important roles in the pre-invasion stages of tumor invasion.
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High-energy Fiber-delivered Ultrashort Pulses on Demand
We describe a nonlinear Er:doped fiber amplification scheme for producing fiber-delivered, 44 fs pulses with 100 kW peak power at arbitrary (0-60 MHz) repetition rate. Subsequent spectral broadening produces 80 THz of bandwidth.
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- Award ID(s):
- 2216021
- PAR ID:
- 10632520
- Publisher / Repository:
- Optica Publishing Group
- Date Published:
- ISBN:
- 978-1-957171-39-5
- Page Range / eLocation ID:
- SM1H.3
- Format(s):
- Medium: X
- Location:
- Charlotte, North Carolina
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1364/CLEO_SI.2024.SM1H.3
