Search bioRxiv⌕ Search

Biology subjects

Tavasso, M.

Publications and source records attributed to Tavasso, M..

3 recordsLinked to original sources

Septins promote breast cancer cell invasion in 3D collagen gels by influencing actin-based protrusion formation

Septins are cytoskeletal proteins that contribute to essential cellular processes such as cell migration and cell division through interactions with the cell membrane and the cytoskeleton. High expression of septins is correlated with breast cancer malignancy and promotes cell invasion, but the molecular complexity of septins interactions has made it challenging to dissect the underlying molecular mechanisms. Here, we used a conditional knockout approach to deplete SEPT7 in the metastatic triple-negative breast cancer cell line Hs578T and examined the role of septin in 3D-matrix invasion of breast cancer cells. We show by spheroid assays that SEPT7 deletion strongly impairs breast cancer cell invasion into collagen gels. Additional single-cell migration studies using 3D collagen gels and microfluidic pillar devices that mimic the pores present in collagen matrices showed that SEPT7 expression regulates confined cell migration through control of cell shape and actin-based protrusions.

cancer biology↗

Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion

Collagen networks form the structural backbone of the extracellular matrix in both healthy and cancerous tissues, exhibiting nonlinear mechanical properties that crucially regulate tissue mechanics and cell behavior. Here, we investigate how the presence of invasive breast cancer cells (MDA-MB-231) influences the polymerization kinetics and mechanics of collagen networks using bulk shear rheology and rheo-confocal microscopy. We show that embedded cancer cells delay the onset of collagen polymerization due to volume exclusion effects. During polymerization, the cells (at 4% volume fraction) cause an unexpected time-dependent softening of the network. We show that this softening effect arises from active remodeling via adhesion and contractility rather than from proteolytic degradation. At higher cell volume fractions, the dominant effect of the cells shifts to volume exclusion, causing a two-fold reduction of network stiffness. Additionally, we demonstrate that cancer cells suppress the characteristic stress-stiffening response of collagen. This effect (partially) disappears when cell adhesion and contractility are inhibited, and it is absent when the cells are replaced by passive hydrogel particles. These findings provide new insights into how active inclusions modify the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy and diseased tissues like invasive tumors.

biophysics↗

Linking metastatic potential and viscoelastic properties of breast cancer spheroids via dynamics compression and relaxation in microfluidics

The growth and invasion of solid tumors are associated with changes in their viscoelastic properties, influenced by both internal cellular factors and physical forces in the tumor microenvironment. Due to the lack of a comprehensive investigation of tumor tissue viscoelasticity, the relationship between such physical properties and cancer malignancy remains poorly understood. Here, the viscoelastic properties of breast cancer spheroids, 3D (in vitro) tumor models, are studied in relation to their metastatic potentials by imposing controlled, dynamic compression within a microfluidic constriction, and subsequently monitoring the relaxation of the imposed deformation. By adopting a modified Maxwell model to extract viscoelastic properties from the compression data, the benign (MCF-10A) spheroids are found to have higher bulk elastic modulus and viscosity compared to malignant spheroids (MCF-7 and MDA-MB-231). The relaxation is characterized by two timescales, captured by a double exponential fitting function, which reveals a similar fast rebound for MCF-7 and MCF-10A. Both the malignant spheroids exhibit similar long-term relaxation and display residual deformation. However, they differ significantly in morphology, particularly in intercellular movements. These differences between malignant spheroids are demonstrated to be linked to their cytoskeletal organization, by microscopic imaging of F-actin within the spheroids, together with cell-cell adhesion strength.

biophysics↗