Mechanical interactions of invasive cancer cells through their substrate evolve from additive to synergistic

Non-contacting, adjacent cancer cells can mechanically interact through their substrate to increase their invasive and migratory capacities that underly metastases-formation. Such mechanical interactions may induce additive or synergistic enhancement of invasiveness, potentially indicating different underlying force-mechanisms. To identify cell–cell-gel interactions, we monitor the time-evolution of three-dimensional traction strains induced by MDA-MB-231 breast cancer cells adhering on physiological-stiffness (1.8 kPa) collagen gels and compare to simulations. Single metastatic cells apply strain energies of 0.2–2 pJ (average 0.51 ± 0.06 pJ) at all observation times (30–174 min) inducing a mechanical volume-of-effect in the collagen gel that is initially (