Structural and mechanical characterization of collagen-hyaluronan hydrogels used to study cancer cell invasion through the bladder wall
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Date
2025-03-06
Authors
Lekka, Małgorzata
Metwally, Sara
Śmiałek-Bartyzel, Justyna
Pabijan, Joanna
Journal Title
Journal ISSN
Volume Title
Publisher
Institute of Nuclear Physics Polish Academy of Sciences
License Type
Creative commons license
Abstract
Collagen-hyaluronic acid (Col-HA) hydrogels are widely studied as biomimetic materials that recapitulate the environmental physical and mechanical properties crucial for understanding the cell behaviour during cancer invasion and progression. Our research focused on Col-HA hydrogels as an environment to study the invasion of bladder cancer cells through the bladder wall. The bladder is a heterogeneous structure composed of three main layers: urothelium (the softest), lamina propria (the stiffest), and the muscle outer layer, with elastic properties lying between the two. Thus, the bladder cancer cells migrate through the mechanically distinct environments. We investigated the impact of Col-HA hydrogel microstructure and rheology on migrating bladder cancer T24 cells from the cancer spheroid surface to the surrounding environment formed from various collagen I and HA concentrations and chemical structures. The designed hydrogels showed variability in pore size, network density, and rheological properties. The migration of bladder cancer cells was inhibited inside hydrogels of ~1kPa Pa storage modulus. The correlation analysis showed that collagen concentration primarily defined the rheological properties of Col-HA hydrogels, but hydrogels can soften or stiffen depending on the type of HA used. Within soft Col-HA hydrogels, cells freely invade the surrounding environment, while its stiffening impedes cell movement and almost inhibits cell migration. Only individual, probably leading, cells are observed at the spheroid edges initiating the invasion. Our findings showed that the rheological properties of the hydrogels dominate in regulating cancer cell migration, providing a platform to study how bladder cancer cells migrate through the heterogenous structure of the bladder wall.
Description
This work was supported by the National Science Center (Poland), project NCN-OPUS no UMO-2021/41/B/ST5/03032 (financing rheological measurements of collagen-based hydrogels, telocollagen (TCol) and thiol-HA-related experiments), and by project NCN-Miniatura 7 no DEC-2023/07/X/ST5/00688 (financing structural analysis of collagen-based hydrogels, atelocollagen (PCol) and fHA-related experiments). Both projects financed cell culture correspondingly.
Keywords
collagen, hyaluronic acid, hydrogels, hydrogel structure rheology, bladder cancer
Citation
Sponsorship:
Polish National Science Centre
Grantnumber:
NCN-OPUS no UMO-2021/41/B/ST5/03032; NCN-Miniatura 7 no DEC-2023/07/X/ST5/00688
License Type
CC0 1.0 Universal