Description
"Cell mechanics serve essential roles in tissue development and cancer progression; cells can sense the mechanical properties of the microenvironment and modulate their physiological functions accordingly. Cellular force signals propagated between cells, however, the influences of cellular force on the mechanical alteration of cell collectives in 3-dimension remains largely underexplored. Considering the critical roles of microglia in glioma progression, using a soft-indentation approach, we studied the impacts of microglia on the mechanical properties of the glioma spheroid (GS) about 300~400 µm in diameter. A few microglia (O(102) cells) attached to the periphery of glioma spheroid (O(104) cells) can modulate the ensemble rheological characteristics of glioma spheroid; no rheological difference was observed was observed in the absence of glioma vitality. In addition to a 2-fold stiffness increase (with about 15% microglia attaching), the results of relaxation measurement suggested that microglia can regulate the viscoelasticity of glioma collectives. By applying the generalized Maxwell model with effective configuration of one elastic element and two Maxwell material constituents in parallel, Showed the alteration of viscoelastic characteristics in glioma collectives .
We further identified the integrity of actin filaments, myosin contractility, and GX43 on the cell membrane are required for signaling the contacts of microglia at periphery to the other cells in the spheroid; the results suggested the importance of intra/intercellular forces in the rheological regulation of 3D multicellular organization. In summary, we showed that the microglia contacts (MgC) of a few microglia are sufficient to alter the mechanical properties of the glioma collective, and the cellular forces interconnect the propagation of a signal from the local microglia. Considering the mechanical properties of the tumor microenvironment are critical in therapeutic resistance and cancer metastasis, our findings highlight the critical roles of physical forces in cell collectives and provide an alternative perspective for the regulations of microglia to glioma."
