The European Physical Journal E ( IF 1.8 ) Pub Date : 2022-05-16 , DOI: 10.1140/epje/s10189-022-00182-6 Lianne Beunk 1 , Gert-Jan Bakker 1 , Diede van Ens 1 , Jeroen Bugter 1 , Floris Gal 1 , Martin Svoren 1 , Peter Friedl 1, 2, 3 , Katarina Wolf 1
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Abstract
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.
Graphic abstract
中文翻译：
癌细胞通过胶原蛋白通道侵袭的肌动球蛋白收缩性要求和相互细胞-组织力学
摘要
间质肿瘤微环境由异质组织的富含胶原蛋白的多孔网络以及通道状结构和界面组成，为入侵细胞提供屏障和引导。侵入 3D 随机多孔胶原网络的肿瘤细胞依赖于肌动球蛋白收缩性来使细胞核变形和移位，而 Rho/Rho 相关激酶依赖性收缩性对于在刚性毛细血管样限制微轨道中的迁移在很大程度上是可有可无的。为了研究这种肌动球蛋白收缩依赖性的二分法是否也适用于生理、可变形的线性胶原环境，我们使用双光子激光烧蚀开发了几乎无障碍的不同横截面的胶原支架微轨道。非常窄和宽的轨道都支持单细胞迁移，当轨道很窄时向外推动胶原蛋白最多四次，或者在轨道时通过高达 40 nN 的牵引力将胶原蛋白壁上的细胞拉到原始直径的 50%很宽，导致轨道宽度优化为单细胞直径。通过合成抑制剂靶向肌动球蛋白收缩性增加了窄轨道中的细胞伸长和核形状变化，并消除了宽和窄轨道的细胞介导的变形。因此，所有通道宽度的迁移速度都降低了，迁移率保持在原始速度的 45-65% 左右。总之，数据表明细胞参与肌动球蛋白收缩以相互调整自身的形态和线性轨道宽度，以达到有效细胞运动的最佳尺寸。
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