Regular Article - Living Systems
Actomyosin contractility requirements and reciprocal cell–tissue mechanics for cancer cell invasion through collagen-based channels
Department of Cell Biology, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands
2 David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Cancer Genomics Center, Utrecht, The Netherlands
Accepted: 4 March 2022
Published online: 16 May 2022
The interstitial tumor microenvironment is composed of heterogeneously organized collagen-rich porous networks as well as channel-like structures and interfaces which provide both barriers and guidance for invading cells. Tumor cells invading 3D random porous collagen networks depend upon actomyosin contractility to deform and translocate the nucleus, whereas Rho/Rho-associated kinase-dependent contractility is largely dispensable for migration in stiff capillary-like confining microtracks. To investigate whether this dichotomy of actomyosin contractility dependence also applies to physiological, deformable linear collagen environments, we developed nearly barrier-free collagen-scaffold microtracks of varying cross section using two-photon laser ablation. Both very narrow and wide tracks supported single-cell migration by either outward pushing of collagen up to four times when tracks were narrow, or cell pulling on collagen walls down to 50% of the original diameter by traction forces of up to 40 nN when tracks were wide, resulting in track widths optimized to single-cell diameter. Targeting actomyosin contractility by synthetic inhibitors increased cell elongation and nuclear shape change in narrow tracks and abolished cell-mediated deformation of both wide and narrow tracks. Accordingly, migration speeds in all channel widths reduced, with migration rates of around 45-65% of the original speed persisting. Together, the data suggest that cells engage actomyosin contraction to reciprocally adjust both own morphology and linear track width to optimal size for effective cellular locomotion.
© The Author(s) 2022
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