Synchronized mechanical oscillations at the cell–matrix interface in the formation of tensile tissue

Abstract

The formation of uniaxial fibrous tissues with defined viscoelastic properties implies the existence of an orchestrated mechanical interaction between the cytoskeleton and the extracellular matrix. This study addresses the nature of this interaction. The hypothesis is that this mechanical interplay underpins the mechanical development of the tissue. In embryonic tendon tissue, an early event in the development of a mechanically robust tissue is the interaction of the pointed tips of extracellular collagen fibrils with the fibroblast plasma membrane to form stable interface structures (fibripositors). Here, we used a fibroblast-generated tissue that is structurally and mechanically matched to embryonic tendon to demonstrate homeostasis of cell-derived and external strain-derived tension over repeated cycles of strain and relaxation. A cell-derived oscillatory tension component is evident in this matrix construct. This oscillatory tension involves synchronization of individual cell forces across the construct and is induced in each strain cycle by transient relaxation and transient tensioning of the tissue. The cell-derived tension along with the oscillatory component is absent in the presence of blebbistatin, which disrupts actinomyosin force generation of the cell. The time period of this oscillation (60–90 s) is well-defined in each tissue sample and matches a primary viscoelastic relaxation time. We hypothesize that this mechanical oscillation of fibroblasts with plasma membrane anchored collagen fibrils is a key factor in mechanical sensing and feedback regulation in the formation of tensile tissues.

Cell migration driven by long-lived spatial memory

“…We observed two main behaviours: a first population of cells exhibited static spreading, and extended slowly their two ends in opposite directions without net displacement of their centre-of-mass (Figure 1d and Supplementary Video 1), while a second population displayed strikingly regular oscillatory trajectories, with an amplitude that could significantly exceed the cell size (Figure 1e and Supplementary Video 2). While oscillatory patterns in cell migration 29,30 , and more generally in cell dynamics 31,32,33 , have been reported for various cell types, and could be attributed to different intracellular processes, we argue below that the oscillations that we observe have so far unrevealed features, which we show originate from a so far unreported mechanism. Both observed behaviours were approximately equally distributed over the cell population, whereas behaviours that did not fall in these two classes – akin to persistent random motion – remained negligible.…”

Endocytic recycling is central to circadian collagen fibrillogenesis and disrupted in fibrosis

“…Whilst collagen fibrils have been located within fibripositors at the plasma membrane by electron microscopy, and cell culture studies have highlighted the importance of extrinsic mechanical forces (e.g. see 36–39 ), cell-derived forces 40, 41 , combined mechanical anchoring and TGF β 1 cell activation 42 , and fluid flow 43 in generating an aligned network of collagen fibrils, mechanistic insights into how cells assemble collagen fibrils at the plasma membrane were lacking. Throughout the current study, collagen fibrils and Cy3-colI labelled fibrils were only seen in close proximity to the plasma membrane; fibrils unattached to cells and at distances from cells were not observed.…”

Early Growth Response Genes Increases Rapidly After Mechanical Overloading and Unloading in Tendon Constructs

“…The timing, 5 min, was also chosen based on a previous in vivo experiment . The bioreactor used in this study was custom‐made by David Holmes at the University of Manchester and allows for two constructs to be stretched at the same time by a single‐stepper motor . Loading was performed in pre‐warmed medium (37°C), but the bioreactor was kept at room temperature (23°C).…”