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Table 2 Effects of matrix stiffness on stem cells in two dimensions versus three dimensions

From: Mechanism of regulation of stem cell differentiation by matrix stiffness

 

Stem cell types

Morphology and cytoskeletal organization

Differentiation

Two-dimensional

ESCs

Col I-coated PDMS: 41 to 260 kPa, lower cell perimeter and less spreading; 2,700 kPa, higher cell perimeter, increased spreading and more stress fibers [62]

HyA gel: 1.2 kPa, pancreatic beta cell [9].

Col I-coated PDMS: 2,700 kPa, mesendoderm cell and osteoblast [62]

 

MSCs

FN-coated PAAm gel: 1 to 2 kPa, rounded and unspread; ≥5 kPa, well spread and amassed a large number of stress fibers [63]

Col I gel and Col I-coated gel, 1 kPa, adipocyte and chondrocyte; 15 kPa, smooth muscle cell [64]

Col I gel and Col I-coated PAAm gel: 1 kPa, less spreading and fewer stress fibers; 15 kPa, more spreading and extensive stress fibers [64]

Col I-coated PAAm gel: 0.1 to 1 kPa, neuron; 8 to 17 kPa, myoblast; 25 to 40 kPa, osteoblast [6]

Col I-coated PAAm gel: 0.1 to 1 kPa, branched and filopodia-rich; 8 to 17 kPa, spindle-shaped; 25 to 40 kPa, polygonal [6]

Sulfonate-coated PAAm:1 kPa, chondrocyte [25]

Sulfonate-coated PAAm; 1 kPa, round shapes with less stress fibers but more cortical actins; 150 kPa, spread out with strong expression of stress fibers [25]

 

ASCs

Adipose matrix-coated PAAm gel: 2 kPa, compact, rounded and smaller aspect ratio; 20 to ~40 kPa, more spreading and larger aspect ratio [61].

Adipose matrix-coated PAAm gel: 2 kPa, adipocyte [61]

 

Cardiac stem cells

FN-coated PAAm gel: 12 to 16 kPa, more rounded and forming organized cellular networks with rounded gaps; FN-coated glass: fibroblast-like [42]

FN-coated PAAm gel: 12 to 16 kPa, endothelial cell [42]

 

Mammary progenitor cells

Col I-coated PAAm gel: 0.1 kPa, cobblestone; 4 kPa, more elongated [60]

Col I-coated PAAm gel: 0.1 kPa, luminal epithelial cell; 4 kPa, myoepithelial cell [60]

Three-dimensional

ESCs

Col I gel and matrigel: 0.02 to 0.3 kPa, less neurite outgrowth; 0.5 to 1 kPa, branching and more neurite outgrowth [65]

PLLA, PLGA, PCL coated matrigel: 50 to 100 kPa, ectoderm cell; 100 to 1,000 kPa, endoderm cell; 1,500 to 6,000 kPa, mesoderm cell [7]

Col I gel and matrigel: 0.02 to 0.3 kPa, glial cell; 0.5 to 1 kPa, neuron [65]

 

MSCs

Col I-HyA gel: 1 kPa, spherical and formed colonies; 10 kPa, flattened [66]

PEG-silica thixotropic gel: 7 Pa (τy)a, neuron; 25 Pa (τy) , myoblast; 75 Pa (τy), osteoblast [54]

PEG gel: 0.2 to 59 kPa, spherical, lack of well-defined actin filaments and microtubules [46]

HyA hydrogel: 3.5 kPa, chondrocyte; 53.6 kPa, hypertrophy [48]

Gtn-HPA gel: 0.6 to 2.5 kPa, less spreading, less organized cytoskeletons; 8 to 12 kPa, greater spreading, more organized cytoskeletons and more stable focal adhesions [67]

Col I-HyA gel: 1 kPa, neuron; 10 kPa, glial cell [66]

PEG gel: 0.2 to 59 kPa, osteoblast [46]

Gtn-HPA gel: 0.6 to 2.5 kPa, neuron; 8 to 12 kPa, myoblast [67]

Alginate gel containing RGD: 5, 10, 22, 45, 110 kPa, grossly spherical and morphology are not strongly correlated to matrix stiffness [47]

Col I-coated PEG nanofiber: 2 to 5 kPa, endothelial cell; 8 to 15 kPa, smooth muscle cell [68]

Col I-coated PEG nanofiber: 2 to 5 kPa, less polarized; 8 to 15 kPa, striated, elongated and greater spreading [68]

PCL nanofiber: 7,100 kPa, chondrocyte; PES-PCL nanofiber: 30,600 kPa, osteoblast [59]

PCL nanofiber: 7,100 kPa, rounded; PES-PCL nanofiber: 30,600 kPa, spread and higher stress fiber density [59]

 

Myoblasts

TG-Gtn gel: 2 kPa, elongated and branched, mesh-like or extended actin filaments; 14 to 32 kPa, dot-like actin microfilaments with filopodia [49]

TG-Gtn gel: 14 to 32 kPa, osteoblast [49]

  1. aτy (liquefaction stress): the minimum shear stress required to liquefy the gel is used to measure the substrate stiffness. ASC, adipose-derived stem cell; Col I, collagen I; ESC, embryonic stem cell; FN, fibronectin; Gtn-HPA, gelatin-hydroxyphenylpropionic acid; HyA, hyaluronic acid; MSC, mesenchymal stem cell; PAAm, polyacrylamide; PCL, poly(ε-caprolactone); PDMS, polydimethylsiloxane; PEG, poly(ethylene glycol); PES, poly(ether sulfone); PLGA, poly(lactic co-glycolic acid); PLLA, poly(L-lactic acid); RGD, arginine-glycine-aspartate; TG-Gtn, transglutaminase-gelatin.