Figure 1. Physical ECM modules determining cell migration.

Tissue properties determining cell migration, including topology of the ECM and organization of interfaces between tissue structures. A Elastic modulus range present in macromolecular tissue structures. GAG-rich stroma surrounding cell networks, such as brain tissue, is soft (below 1.0 kPa)⁴⁸; loose fibrillar type I and III collagen-based porous protein networks such as dermis and breast scale typically between 0.2 and 2 kPa^111,118. Thicker, more crosslinked collagen bundles in muscle are substantially stiffer (12 kPa)⁴⁸, which reaches the low GPa range in tendon¹⁵³. Basement membranes consisting of type IV collagen and laminins have a stiffness in the higher kPa range, with at least double the stiffness on the epithelial side compared to the stromal side¹⁵⁴. The stiffness of calcified tissue, including cortical bone, can go up to 15 GPa¹⁵⁵. B Principal ECM geometries defining mechanical cell migration interfaces (green) including 1D, 2D and 3D organization and nanotopology. C Baseline porosity range, relative to cell size and deformability, and hydrostatic pressure induced reversible swelling and mechanical alterations in fibrillar ECM. D Irreversible changes induced by physical or biochemical factors. Direction of physical deformation denoted by green arrows.