Cells have feelings too: Dissecting in situ cell-ECM force interactions in 3D culture models and in Danio rerio

FARE Award Winner

Authors

• BH Blehm
• A Devine
• JR Staunton
• K Tanner

Abstract

The physical properties of the microenvironment, including the stiffness, dimension, and topography have profound impacts on cell fate, tissue assembly and malignancy. However, delineating the complex interplay between cells and their physical microenvironment is challenging using existing techniques. What is needed is the ability to resolve and quantitate minute forces that cells sense in the local environment (microns) within thick tissue (mm). 3D culture models approximate in vivo architecture and signaling cues, allowing for real time characterization of cell-ECM dynamics. Using an optical tweezers we performed active microrheology to measure material properties at length scales unobtainable by bulk rheology. Refractive microspheres are used as local sensors to measure the local displacement both due to Brownian motion and force applied by the optical trap, which are then converted into physical properties. We demonstrate the ability to generate stress-strain relationships in thick gels at frequencies relevant to cellular processes, allowing us to quantify minute forces. We spatially map the viscoelastic properties of the microenvironment in vitro and in vivo during tumorigenesis. We first determined that the forces that cells sense or transmit are short-range, and are quickly dissipated within the hydrogel. We then applied our technique in live zebrafish, Danio rerio, mapping the viscoelastic properties of the fish tissue in regions where human tumor cells were actively proliferating. This is the first time in situ optical trap calibration and micron-scale mechanical characterization has been applied in a thick hydrogel and in vivo, accurately characterizing physical determinants of the local microenvironment.

Scientific Focus Area: Biomedical Engineering and Biophysics

This page was last updated on Friday, March 26, 2021