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  Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Mahajan, V., Beck, T., Gregorczyk, P., Ruland, A., Alberti, S., Guck, J., et al. (2021). Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy. Cancers / Molecular Diversity Preservation International (MDPI), 13(21): 5549. doi:10.3390/cancers13215549.

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Cancers 2021 Mahajan.pdf (Publisher version), 4MB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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 Creators:
Mahajan, Vaibhav1, Author
Beck, Timon1, 2, Author
Gregorczyk, Paulina1, Author
Ruland, André3, Author
Alberti, Simon1, Author
Guck, Jochen2, 4, Author           
Werner, Carsten3, Author
Schlüßler, Raimund1, Author
Taubenberger, Anna V.1, Author
Affiliations:
1Technische Universität Dresden, ou_persistent22              
2Guck Division, Max Planck Institute for the Science of Light, Max Planck Society, ou_3164416              
3external, ou_persistent22              
4Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society, ou_3164414              

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 Abstract: Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)-degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids’ cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids’ mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression.

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Language(s): eng - English
 Dates: 2021-11-05
 Publication Status: Published online
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 Identifiers: DOI: 10.3390/cancers13215549
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Title: Cancers / Molecular Diversity Preservation International (MDPI)
  Abbreviation : Cancers (Basel)
Source Genre: Journal
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Publ. Info: Basel : Molecular Diversity Preservation International (MDPI)
Pages: - Volume / Issue: 13 (21) Sequence Number: 5549 Start / End Page: - Identifier: ISSN: 2072-6694
CoNE: https://pure.mpg.de/cone/journals/resource/2072-6694