Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 4, Issue 2, Pages 468-472Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b01005
Keywords
cytoskeletal tension; degradation; matrix metalloproteinase; multiple particle tracking microrheology
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Funding
- National Institute of General Medical Sciences of the National Institutes of Health [R15GM119065]
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Human mesenchymal stem cells (hMSCs) are encapsulated in synthetic matrix metalloproteinase (MMP) degradable poly(ethylene glycol)-peptide hydrogels to characterize cell-mediated degradation of the pericellular region using multiple particle tracking microrheology. The hydrogel scaffold is degraded by cell-secreted enzymes and cytoskeletal tension. We determine that cell-secreted enzymatic degradation is the main contributor to changes in the pericellular region, with cytoskeletal tension playing a minimal role. Measured degradation profiles for untreated and myosin II inhibited hMSCs have the highest cross-link density around the cell. We hypothesize that cells are also secreting tissue inhibitor of metalloproteinases (TIMPs) to inhibit MMPs, which allow cell spreading and attachment prior to motility. We develop a Michaelis Menten competitive enzymatic inhibition model which accurately describes the degradation profile due to MMP-TIMP unbinding.
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