High-Frequency Mechanical Properties of Tumors Measured by Brillouin Light Scattering

Abstract

The structure of tumors can be recapitulated as an elastic frame formed by the connected cytoskeletons of the cells invaded by interstitial and intracellular fluids. The low-frequency mechanics of this poroelastic system, dictated by the elastic skeleton only, control tumor growth, penetration of therapeutic agents, and invasiveness. The high-frequency mechanical properties containing the additional contribution of the internal fluids have also been posited to participate in tumor progression and drug resistance, but they remain largely unexplored. Here we use Brillouin light scattering to produce label-free images of tumor microtissues based on the high-frequency viscoelastic modulus as a contrast mechanism. In this regime, we demonstrate that the modulus discriminates between tissues with altered tumorigenic properties. Our micrometric maps also reveal that the modulus is heterogeneously altered across the tissue by drug therapy, revealing a lag of efficacy in the core of the tumor. Exploiting high-frequency poromechanics should advance present theories based on viscoelasticity and lead to integrated descriptions of tumor response to drugs.

Picosecond ultrasounds as elasticity probes in neuron-like cells models

“…In the case of tumors, the increase in rigidity could be related to various factors, including an increase in the modulus of elasticity of transformed cells due to cellular disturbances. This leads to tumors being generally stiffer than normal tissues 9,10 .…”

Brillouin microscopy: an emerging tool for mechanobiology

“…a porous elastic meshwork of (inter-connected) solid components (cytoskeleton, organelles, macromolecules) bathed in an interstitial fluid (cytosol). This framework has recently been extended to describe the structure of and metastatic potential of tumors 64 . In the extracellular environment, extracellular matrices can also be described as elastic networks embedded in extracellular fluid.…”

“…At a cellular level, the presence of a lipid-rich layer surrounding amyloid plaques, as well as the level of hydration, have been shown to influence the line-width 52 . At the tissue level, the level of cell-cell adhesion has been associated with a modified viscosity assessed through an increase in Brillouin line-width in cellular aggregates 64 . However, for any linewidth interpretations, it is important to discriminate viscous effects from other factors that lead to a linewidth broadening, such as e.g.…”

Microscale Interrogation of 3D Tissue Mechanics

“…Mechanical properties and states can also directly affect a material's optical properties, which can therefore be used to probe tissue mechanics. One of such approaches with increasing application in mapping tissue mechanical properties is Brillouin light scattering microscopy based on acousto-optic interaction (Scarcelli et al, 2013(Scarcelli et al, , 2015Elsayad et al, 2016;Margueritat et al, 2019). Thermally excited sound waves inherent to a material propagate as acoustic "phonons, " which interact with optical "photons" of the probing laser, thus, resulting in light scattering and a spectral shift, known as the Brillouin frequency shift (BFS).…”