Mapping cellular-scale internal mechanics in 3D tissues with thermally responsive hydrogel probes

Local tissue mechanics play a critical role in cell function, but measuring these properties at cellular length scales in living 3D tissues can present considerable challenges. Here we present thermoresponsive, smart material microgels that can be dispersed or injected into tissues and optically ass...

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Bibliographic Details
Published in:Nature communications 2020-09, Vol.11 (1), p.4757-4757, Article 4757
Main Authors: Mok, Stephanie, Al Habyan, Sara, Ledoux, Charles, Lee, Wontae, MacDonald, Katherine N., McCaffrey, Luke, Moraes, Christopher
Format: Article
Language:English
Subjects:
14/63
631/1647/2204
631/61
639/166/985
9/10
Animals
Biomechanical Phenomena
Biosensing Techniques - instrumentation
Biosensing Techniques - methods
Cell Line
Elasticity
Humanities and Social Sciences
Humans
Hydrogels - chemistry
Mice
Models, Biological
multidisciplinary
Neoplasms, Experimental - pathology
Science
Science (multidisciplinary)
Spheroids, Cellular - pathology
Spheroids, Cellular - physiology
Temperature
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Summary:Local tissue mechanics play a critical role in cell function, but measuring these properties at cellular length scales in living 3D tissues can present considerable challenges. Here we present thermoresponsive, smart material microgels that can be dispersed or injected into tissues and optically assayed to measure residual tissue elasticity after creep over several weeks. We first develop and characterize the sensors, and demonstrate that internal mechanical profiles of live multicellular spheroids can be mapped at high resolutions to reveal broad ranges of rigidity within the tissues, which vary with subtle differences in spheroid aggregation method. We then show that small sites of unexpectedly high rigidity develop in invasive breast cancer spheroids, and in an in vivo mouse model of breast cancer progression. These focal sites of increased intratumoral rigidity suggest new possibilities for how early mechanical cues that drive cancer cells towards invasion might arise within the evolving tumor microenvironment. Local mechanical properties are important to cellular function; but conventional measurement techniques are limited in intact, living, 3D tissues. Here, the authors report on swellable hydrogel microparticles to monitor mechanical properties in situ via a temperature change.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-18469-7