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

Nat Commun. 2020 Sep 21;11(1):4757. doi: 10.1038/s41467-020-18469-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena*
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Cell Line
  • Elasticity
  • Humans
  • Hydrogels / chemistry*
  • Mice
  • Models, Biological
  • Neoplasms, Experimental / pathology
  • Spheroids, Cellular / pathology
  • Spheroids, Cellular / physiology
  • Temperature

Substances

  • Hydrogels

Grants and funding