Abstract
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.
Highlights
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
The thermoresponsive diameter change was independent of μTAM size, and tunable based on the hydrogel formulation (Supplementary Fig. 2)
Whereas sensitive analysis techniques such as atomic force microscopy[56] and microrheology[57] may capture these spatial resolutions they do not approximate the stroke lengths generated by real cells, and measure mechanical properties of the material in a strain regime that may or may not be relevant to cellular mechanosensing and microenvironmental interrogation
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. Serwane et al recently developed an intriguing strategy to measure tissue mechanics with injectable, cell-sized, magnetic oil droplets, that deform in response to applied magnetic fields to quantify local tissue mechanics in soft tissues such as zebrafish embryos[27] This powerful approach provides unique insight into highly local evolution of tissue mechanics during development, but the small droplet volumes allow only very low magnetic actuation forces, limited stroke lengths, and can only measure stiffnesses of
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