The compaction of gels by cells: a case of collective mechanical activity.

To understand mechanotransduction, purely mechanical phenomena resulting from the crosstalk between contractile cells and their elastic surroundings must be distinguished from adaptive responses to mechanical cues. Here, we revisit the compaction of freely suspended collagen gels by embedded cells, where a small volume fraction of cells (osteoblasts and fibroblasts) compacts the surrounding matrix by two orders of magnitude. Combining micropatterning with time-lapse strain mapping, we find gel compaction to be crucially determined by mechanical aspects of the surrounding matrix. First, it is a boundary effect: the compaction propagates from the edges of the matrix into the bulk. Second, the stress imposed by the cells irreversibly compacts the matrix and renders it anisotropic as a consequence of its nonlinear mechanics and the boundary conditions. Third, cell polarization and alignment follow in time and seem to be a consequence of gel compaction, at odds with current mechanosensing conceptions. Finally, our observation of a threshold cell density shows gel compaction to be a cooperative effect, revealing a mechanical interaction between cells through the matrix. The intricate interplay between cell contractility and surrounding matrix mechanics provides an important organizing principle with implications for many physiological processes such as tissue development.