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 (<60 min from seeding) on the cell-volume scale (∼3000 µm³) and on average increases with time from cell seeding. When cells adhere closely adjacent, at short times (<60 min) we distinguish the additive contributions of neighboring cells to the strains, while at longer times strain fields are synergistically amplified and may facilitate increased cooperative/collective cancer-cell-invasiveness. The results of well-spaced and closely adjacent cells at short times match our simulations of additive deformations induced by radially applied strains with experimentally based inverse-distance decay. We thus reveal a time-dependent evolution from additive to synergistic interactions of adjacently adhering cells that may facilitate metastatic invasion.

非接触的相邻癌细胞可以通过它们的基质进行机械相互作用，以增加它们的侵袭和迁移能力，这是转移形成的基础。这种机械相互作用可能会导致侵入性的附加或协同增强，可能表明不同的潜在力机制。为了识别细胞 - 细胞 - 凝胶相互作用，我们监测由粘附在生理刚度 (1.8 kPa) 胶原凝胶上的 MDA-MB-231 乳腺癌细胞诱导的三维牵引应变的时间演变，并与模拟进行比较。单个转移细胞在所有观察时间（30-174 分钟）施加 0.2-2 pJ（平均 0.51 ± 0.06 pJ）的应变能，从而在最初（<60 分钟后接种）的胶原凝胶中产生机械效应体积在细胞体积尺度 (∼3000 µm ³) 并且平均而言随着细胞接种的时间而增加。当细胞紧密相邻时，在短时间内（<60 分钟），我们区分相邻细胞对菌株的附加贡献，而在更长的时间内，菌株场被协同放大，并可能促进合作/集体癌细胞侵袭性的增加。短时间间隔良好且紧密相邻的单元的结果与我们对由径向施加的应变引起的附加变形的模拟与基于实验的反距离衰减相匹配。因此，我们揭示了从可促进转移性侵袭的相邻粘附细胞的累加相互作用到协同相互作用的时间依赖性演变。