Figure 5. Proposed model for strain amplification and heterogeneity at larger spatial scales.

At the molecular level, a nanometer scale acto-myosin sliding mechanism creates a piconewton scale force. At the cell and nuclear level, strains depend mostly on the actions of the molecular scale. This allows the strain to be locally dependent on molecular machinery and highly regulated. At increasingly larger scale, many individual acto-myosin units combine to work to generate a higher amount of force. However, the addition of passive elements at each hierarchical level determines the strain at higher levels and depends on the geometry and combined material properties of the active and passive elements and force at that scale. Thus, at the subcellular level, passive titin and non-sarcomere proteins add to the acto-myosin active machinery. At the tissue scale, it is further added by other passive elements, such as extracellular matrix, collagen, and endomysium, and finally, at the organ scale, by perimysium and other geometrical factors, such as collagen architecture and pennation angle. Thus, from small to large scale, apparent ‘emergent behavior’ appears.