Figure 1. Universal scale of micro-stiffness for tissues.
A. The body is composed of tissues that vary over log scales of stiffness. Atomic force microscopy can be used to probe the stiffness of tissues at a micro-scale similar to that probed by cells. Soft tissues have orders of magnitude lower stiffness than glass or tissue culture plastic. Adapted from [89].
B. Gels can be engineered to mimic the stiffness of tissues found in vivo. AFM indentations on gel or tissue yield the elastic properties and fit well with models when probed at 1 mm/sec that is relevant to cell mechanics. The predictable scaling over log scales of gel elasticity with polymer density or crosslinking in gels verifies the mechanical properties of in vitro gel systems. Adapted from [90].
C. Polyacrylamide gels are covalently attached to glass and then coated with a thin layer of covalently attached collagen-I to functionalize the gel which becomes inert and stable [91]. Gel systems can be characterized microscopically and mechanically, which demonstrates homogeneity by the high agreement between micro-elasticity measured by AFM and bulk elasticity measured with rheology, unaltered by collagen coating.
D. Projected area of MSCs versus matrix elastic modulus of both hylaronic acid (HA) and polyacrylamide (PA) gels coated with collagen I. The projected area can be fit with the a Hill equation: A = AmaxB/(Em+ E). Where A is the calculated projected area of the cell, Amax is the maximum area of the cell on a rigid substrate, B is a constant where B = Em(Amax— Amin), and Em is the matrix elasticity where the area is the mid-point between the maximum and minimum (and the delineation between soft and stiff gels). On the right is MSC projected area vs surface concentration of collagen l, with the focus of this review on the saturated portion of the curve. Adapted from [38].