Mechanical explanation for simultaneous formation of different tissues in an organ morphogenesis

An interesting recent finding is that, in a medium of nearly linear elastic materials, the stem cell differentiation responds to the Young’s modulus of elasticity. It is discussed here that the more general mechanical identifier of differentiation is indeed the stiffness (rather than the Young’s modulus). Specifically, for nonlinear (and thus more realistic/physiologically mimetic) materials the stiffness experienced by the cells is affected by the intracellular distance and hence by the local density of the cells. It is proposed here that the stiffness-directed differentiation is affected not only by the substrate elasticity but also by the cell density and diffusion effects (relocations). Thus, it is suggested that nonlinear effects actually augment fascinating more versatile capabilities to the stiffness-directed differentiation compared to what was supposed by the traditional linear elastic materials. In particular, it is argued how such modified stiffness-directed differentiation criteria can explain simultaneous differentiation paths leading to the formation of an organ. Formation of organs like a limb requires simultaneous formation of different tissues from the hardest (central cartilage and bone) to softest ones (vascular networks of blood vessels and neurons) at correct locations. This means that while the pattern of initial stem cells is changing, they should follow different differentiation paths at the same time on the same substrate (a primary limb cross section, for instance). Here, it is shown that the distribution and relocation of the stem cells affect their sensing of the surrounding mechanics and hence their differentiation. This means various kinds of tissues automatically form, while the stem cells are redistributing and/or relocating.