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.
Subject(s)
Models, Biological , Neoplasms/pathology , Biomechanical Phenomena , Cell Line, Tumor , Cytoskeleton/chemistry , Cytoskeleton/pathology , Elasticity , HCT116 Cells , Humans , Neoplasms/chemistry , Scattering, Radiation , Spheroids, Cellular/chemistry , Spheroids, Cellular/pathologyABSTRACT
Our study proposes a new way to observe and explain the presence of extended plasmonic modes in disordered semi-continuous metal films before the percolation threshold. Attenuated total reflection spectroscopy allows us to follow the transition of plasmon modes from localized to delocalized resonances, but also reveals unobserved collective plasmon modes. These bright modes with out-of-plane polarization are transverse collective plasmonic resonances. By increasing the density of metallic nanoparticles in a wavelength scale, we observe an angular squeezing and spectral broadening of these modes. This behavior can be explained considering that transverse localized surface plasmon resonances of each nanoparticle, all resonant, interact in a collective and coherent way via a common confined light mode: the evanescent wave. These many-body resonances, which have never been clearly identified in such disordered semi-continuous metal films, can be described by analogy with atomic physics as superradiant modes. Our first simulations, using dyadic Green's formalism, demonstrate the existence of this mode for a dense array of plasmonic systems. In this regime, the radiation rate of the superradiant mode increases with the number of tied dipoles. This explains the spectral broadening observed in our work and constitutes the first manifestation of superradiance mode in plasmonic random structure.
ABSTRACT
The acoustic vibrations of single monomers and dimers of gold nanoparticles were investigated by measuring for the first time their ultralow-frequency micro-Raman scattering. This experiment provides access not only to the frequency of the detected vibrational modes but also to their damping rate, which is obscured by inhomogeneous effects in measurements on ensembles of nano-objects. This allows a detailed analysis of the mechanical coupling occurring between two close nanoparticles (mediated by the polymer surrounding them) in the dimer case. Such coupling induces the hybridization of the vibrational modes of each nanoparticle, leading to the appearance in the Raman spectra of two ultralow-frequency modes corresponding to the out-of-phase longitudinal and transverse (with respect to the dimer axis) quasi-translations of the nanoparticles. Additionally, it is also shown to shift the frequency of the quadrupolar modes of the nanoparticles. Experimental results are interpreted using finite-element simulations, which enable the unambiguous identification of the detected modes and despite the simplifications made lead to a reasonable reproduction of their measured frequencies and quality factors. The demonstrated feasibility of low-frequency Raman scattering experiments on single nano-objects opens up new possibilities to improve the understanding of nanoscale vibrations with this technique being complementary with single nano-object time-resolved spectroscopy as it gives access to different vibrational modes.