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Abstract Multicellular spheroids have shown great promise in 3D biology. Many techniques exist to form spheroids, but how cells take mechanical advantage of native fibrous extracellular matrix (ECM) to form spheroids remains unknown. Here, we identify the role of fiber diameter, architecture, and cell contractility on spheroids’ spontaneous formation and growth in ECM-mimicking fiber networks. We show that matrix deformability revealed through force measurements on aligned fiber networks promotes spheroid formation independent of fiber diameter. At the same time, larger-diameter crosshatched networks of low deformability abrogate spheroid formation. Thus, designing fiber networks of varying diameters and architectures allows spatial patterning of spheroids and monolayers simultaneously. Forces quantified during spheroid formation revealed the contractile role of Rho-associated protein kinase in spheroid formation and maintenance. Interestingly, we observed spheroid–spheroid and multiple spheroid mergers initiated by cell exchanges to form cellular bridges connecting the two spheroids. Unexpectedly, we found large pericyte spheroids contract rhythmically. Transcriptomic analysis revealed striking changes in cell–cell, cell–matrix, and mechanosensing gene expression profiles concordant with spheroid assembly on fiber networks. Overall, we ascertained that contractility and network deformability work together to spontaneously form and pattern 3D spheroids, potentially connecting in vivo matrix biology with developmental, disease, and regenerative biology.
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Aromatic carbohydrate amphiphile disrupts cancer spheroids and prevents relapse
Spheroids recapitulate the organization, heterogeneity and microenvironment of solid tumors. Herein, we targeted spatiotemporally the accelerated metabolism of proliferative cells located on the spheroid surface that ensure structure maintenance and/or growth. We demonstrate that phosphorylated carbohydrate amphiphile acts as a potent antimetabolite due to glycolysis inhibition and to in situ formation of supramolecular net around spheroid surface where alkaline phosphatase is overexpressed. The efficiency of the treatment is higher in spheroids as compared to the conventional 2D cultures because of the 2-fold higher expression of glucose transporter 1 (GLUT1). Moreover, treated spheroids do not undergo following relapse.
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- Award ID(s):
- 1808143
- PAR ID:
- 10382292
- Date Published:
- Journal Name:
- Nanoscale
- Volume:
- 12
- Issue:
- 37
- ISSN:
- 2040-3364
- Page Range / eLocation ID:
- 19088 to 19092
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0nr05008c
