Extracellular Stiffness Modulates the Expression of Functional Proteins and Growth Factors in Endothelial Cells.
Angiogenesis, the formation of blood vessels from pre-existing ones, is of vital importance during the early stages of bone healing. Extracellular stiffness plays an important role in regulating endothelial cell behavior and angiogenesis, but how this mechanical cue affects proliferation kinetics, gene regulation, and the expression of proteins implicated in angiogenesis and bone regeneration remains unclear. Using collagen-coated polyacrylamide (PAAm) hydrogels, human umbilical vein endothelial cells (HUVECs) are exposed to an environment that mimics the elastic properties of collagenous bone, and cellular proliferation and gene and protein expressions are assessed. The proliferation and gene expression of HUVECs are not differentially affected by culture on 3 or 30 kPa PAAm hydrogels, henceforth referred to as low and high stiffness gels, respectively. Although the proliferation and gene transcript levels remain unchanged, significant differences are found in the expressions of functional proteins and growth factors implicated both in the angiogenic and osteogenic processes. The down-regulation of the vascular endothelial growth factor receptor-2 protein with concomitant over-expression of caveolin-1, wingless-type 2, bone morphogenic protein 2, and basic fibroblast growth factor on the high stiffness PAAm hydrogel suggests that rigidity has a pro-angiogenic effect with inherent benefits for bone regeneration.
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Lívia
L
Santos
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Gregor
G
Fuhrmann
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Maya
M
Juenet
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Nadav
N
Amdursky
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Christine-Maria
CM
Horejs
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Paola
P
Campagnolo
Department of Materials, Imperial College London, London, SW7 2AZ, UK.|Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.|Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Molly M
MM
Stevens
Young's modulus; angiogenesis; bone regeneration; endothelial cells; extracellular rigidity