Institut Lumière Matière, UMR5306, Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne, France.
Université de Lyon, Université Lyon 1, INSERM U1052, CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon, France.
Phys Rev Lett. 2019 Jan 11;122(1):018101. doi: 10.1103/PhysRevLett.122.018101.
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.
肿瘤的结构可以被概括为一个弹性框架,由间质和细胞内液体侵入的细胞的连接细胞骨架形成。这个多孔弹性系统的低频力学特性仅由弹性骨架决定,控制肿瘤生长、治疗剂渗透和侵袭性。高频力学特性包含内部流体的附加贡献也被假定参与肿瘤进展和耐药性,但它们在很大程度上仍未得到探索。在这里,我们使用布里渊光散射根据高频粘弹性模量作为对比机制来产生肿瘤微组织的无标记图像。在这个范围内,我们证明了模量可以区分具有改变的致瘤特性的组织。我们的微尺度图谱还表明,药物治疗会使组织的模量在整个组织中不均匀地改变,从而揭示了肿瘤核心的疗效滞后。利用高频渗透力学应该会推进基于粘弹性的现有理论,并导致对肿瘤对药物反应的综合描述。