Actomyosin contractility-dependent matrix stretch and recoil induces rapid cell migration

Abstract

Cells select from a diverse repertoire of migration strategies. Recent developments in tunable biomaterials have helped identify how extracellular matrix properties influence migration, however, many settings lack the fibrous architecture characteristic of native tissues. To investigate migration in fibrous contexts, we independently varied the alignment and stiffness of synthetic 3D fiber matrices and identified two phenotypically distinct migration modes. In contrast to stiff matrices where cells migrated continuously in a traditional mesenchymal fashion, cells in deformable matrices stretched matrix fibers to store elastic energy; subsequent adhesion failure triggered sudden matrix recoil and rapid cell translocation. Across a variety of cell types, traction force measurements revealed a relationship between cell contractility and the matrix stiffness where this migration mode occurred optimally. Given the prevalence of fibrous tissues, an understanding of how matrix structure and mechanics influences migration could improve strategies to recruit repair cells to wound sites or inhibit cancer metastasis.

Robust and Precise Wounding and Analysis of Engineered Contractile Tissues

“…40 A mechanical basis for rapid closure is also conceptually consistent with recent studies demonstrating that cells can migrate through a matrix via a slingshot action, in which tension is first built up by tissue deformation, and the elastic energy stored in the matrix can be directed on release of cell adhesion to enhance migration rates. 53 Analogously, actively wounding the tissue causes retraction at the wound edge, which increases local matrix density, stiffness, and circumferential hoop stress (Fig. 3E, F).…”

Blebbistatin Inhibits Neomycin-Induced Apoptosis in Hair Cell-Like HEI-OC-1 Cells and in Cochlear Hair Cells

“…Blebbistatin is a myosin II inhibitor, and it regulates microtubule assembly and myosin-actin interactions. The activity of blebbistatin on the cytoskeleton has been shown to be involved in the regulation of cell structure, morphology (Yoon et al, 2019), and migration (Hu et al, 2019;Wang et al, 2019) and to maintain the survival and growth of stem cells (Zhao et al, 2015) and to reduce oxidative stressinduced apoptosis. Blebbistatin protects Lgr5+ stem cells against colitis-induced epithelium injury in gastrointestinal tissues through the Myh9-Rac1-PAK1-Akt pathway (Zhao et al, 2015) and induces cell migration through myosin-II-related matrix stretch and recoil (Vicente-Manzanares et al, 2009).…”

Computational estimates of mechanical constraints on cell migration through the extracellular matrix

“…Needless to say, we have not investigated how cells change migration mode in response to the ECM properties [54], and we have not considered other modes of motility, such as blebbing [30] and chimneying [55]. More advanced problems, like mechanosensing [56], ECM remodeling and its feedback with cell mechanics [57], coordination of traction forces with ECM stiffness [11], proteolytic activity to melt down and rarefy the ECM in front of the cell [2,5,58], and nuclear damage in passages through small ECM gaps [59] are beyond the scope of the model.…”

“…It appears from the images in [9] that the cells generate ECM deformations, which then propel the cells forward because the ECM is elastic and its deformations store elastic energy that can be released to propel the cell [10]. Another example of generating the ECM deformations and then harnessing them to create locomotion was recently reported in [11].…”