000084220 001__ 84220 000084220 005__ 20201113085627.0 000084220 0247_ $$2doi$$a10.1016/j.bpj.2019.02.029 000084220 0248_ $$2sideral$$a111260 000084220 037__ $$aART-2019-111260 000084220 041__ $$aeng 000084220 100__ $$0(orcid)0000-0002-8656-7846$$aCóndor, M. 000084220 245__ $$aBreast cancer cells adapt contractile forces to overcome steric hindrance 000084220 260__ $$c2019 000084220 5060_ $$aAccess copy available to the general public$$fUnrestricted 000084220 5203_ $$aCell migration through the extracellular matrix is governed by the interplay between cell-generated propulsion forces, adhesion forces, and resisting forces arising from the steric hindrance of the matrix. Steric hindrance in turn depends on matrix porosity, matrix deformability, cell size, and cell deformability. In this study, we investigate how cells respond to changes in steric hindrance that arise from altered cell mechanical properties. Specifically, we measure traction forces, cell morphology, and invasiveness of MDA-MB 231 breast cancer cells in three-dimensional collagen gels. To modulate cell mechanical properties, we either decrease nuclear deformability by twofold overexpression of the nuclear protein lamin A or we introduce into the cells stiff polystyrene beads with a diameter larger than the average matrix pore size. Despite this increase of steric hindrance, we find that cell invasion is only marginally inhibited, as measured by the fraction of motile cells and the mean invasion depth. To compensate for increased steric hindrance, cells employ two alternative strategies. Cells with higher nuclear stiffness increase their force polarity, whereas cells with large beads increase their net contractility. Under both conditions, the collagen matrix surrounding the cells stiffens dramatically and carries increased strain energy, suggesting that increased force polarity and increased net contractility are functionally equivalent strategies for overcoming an increased steric hindrance. 000084220 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000084220 590__ $$a3.854$$b2019 000084220 591__ $$aBIOPHYSICS$$b15 / 71 = 0.211$$c2019$$dQ1$$eT1 000084220 592__ $$a1.833$$b2019 000084220 593__ $$aBiophysics$$c2019$$dQ1 000084220 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000084220 700__ $$aMark, C. 000084220 700__ $$aGerum, R.C. 000084220 700__ $$aGrummel, N.C. 000084220 700__ $$aBauer, A. 000084220 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, J.M.$$uUniversidad de Zaragoza 000084220 700__ $$aFabry, B. 000084220 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est. 000084220 773__ $$g116, 7 (2019), 1305-1312$$pBiophys. j.$$tBIOPHYSICAL JOURNAL$$x0006-3495 000084220 8564_ $$s1490012$$uhttps://zaguan.unizar.es/record/84220/files/texto_completo.pdf$$yPostprint 000084220 8564_ $$s83011$$uhttps://zaguan.unizar.es/record/84220/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000084220 909CO $$ooai:zaguan.unizar.es:84220$$particulos$$pdriver 000084220 951__ $$a2020-11-13-08:47:20 000084220 980__ $$aARTICLE