Mechanobiological studies of cell assemblies have generally focused on cells that

Mechanobiological studies of cell assemblies have generally focused on cells that are in principle identical. development where spatial gradients of JTK12 morphogens initiate cellular development. In the 1970s Wagner and Horner1 motivated by the suggestion of Alefeld2 combined elasticity theory with statistical mechanics to predict the elastically mediated interactions of small atoms in metals. The macroscopic lattice deformations induced by these elastic inclusions3 are long-ranged (dipolar) and the consequent diffusion and assembly of the atoms depend on the sample shape. Similar ideas have recently been applied to living cells that adhere to an extracellular matrix (ECM)4. These interact through mutual contractile deformations5 of the underlying matrix by forces generated by molecular motors (myosin) that act on the cytoskeleton a network of crosslinked filamentous biopolymers that forms the structural framework of a cell6. Due to acto-myosin activity4 the cells contract the matrix and each cell can be idealized as a contractile force dipole5 in analogy with inclusions in solids. However due to the active nature of this contractility the cell can regulate the dipole strength and symmetry and here lies an important difference between live and dead matter. The field of mechanobiology or “cell mechanics” to be more specific focuses on how cells generate sense and respond to mechanical stimuli such as forces7. Recent advances in this field suggest that the mechanical microenvironment of a cell particularly its rigidity8 9 influences key aspects of cell structure and functionality. This demonstrates the importance of elastic interactions that can be mediated by deformations of the cytoskeleton within a cell or of the substrate or extra-cellular matrix between cells. These ideas have been used to explain the experimentally observed dependence of organization of the cytoskeleton on MLN4924 substrate stiffness4 10 11 12 In addition to the role of the mechanical environment on physico-chemical properties such as the organization of the cytoskeleon or cell-cell forces13 measurements of the role of mechanics in the differentiation14 and development of the cytoskeleton of stem cells10 15 and in gene expression in mature cells16 have demonstrated that biological function can be strongly modulated by the sensitivity and response of cells to mechanical cues. While the mechanobiology community has typically treated assemblies of isolated adherent cells that are in principle homogeneously contractile this is in fact not always the case as in cell MLN4924 monolayers important in motility and wound healing assays17. The cells at the periphery of the monolayer are in principle different from those closer to the center18. Such assemblies are of course subject to internal mechanical forces. The results presented in this paper suggest that these mechanical forces that originate in contractility can be coupled to biochemical diffusion that can further influence the contractility of the monolayer an effect that though plausible is yet to be investigated in a mechanobiological context. In addition such effects may be relevant to pattern formation in tissue development. All of these motivate our investigation MLN4924 of the role of gradients of biochemical signaling molecules and their feedback with cellular contractility. Inspired by this idea from developmental biology but considering cells in culture as a first step we denote such molecules that induce cytoskeletal contractility in a concentration-dependent manner as “mechanogens” (analogous to “morphogens” in embryo development19). In addition to their role in the structural organization of the cellular cytoskeleton of isolated cells elastic interactions between cells provides an additional strategy for long-ranged inter-cellular signaling which can be much faster than the diffusion of chemical signals20 21 The idea that mechanics via the forces22 23 and flows24 25 generated by active cellular processes MLN4924 interacts with chemical signaling to regulate various aspects of development has led some authors to suggest a “mechanochemical basis” of morphogenesis26 27 28 While the crucial role of physical forces and dynamics in aspects of development was historically appreciated29 it has only recently begun to be quantified26 in specific model systems. In contrast with prior mechanochemical models that consider either the hydrodynamic flow of cytoskeletal elements25 or the hydrostatic mechanical pressure30 created.