Macromolecular dextran sulfate facilitates extracellular matrix deposition by electrostatic interaction independent from a macromolecular crowding effect
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AbstractA faithful reconstruction of the native cellular microenvironment is instrumental for tissue engineering. Macromolecular crowding (MMC) empowers cells to deposit their own extracellular matrix (ECM) in greater amounts, and thus contributes to building tissue-specific complex microenvironments in vitro. Dextran sulfate (DxS, 500 kDa), a semi-synthetic sulfated polyglucose, was shown previously at a fractional volume occupancy (FVO) of 5.2% (v/v; 100 μg/ml) to act as a potent molecular crowding agent in vitro. When added to human mesenchymal stromal cell (MSC) cultures, DxS enhanced fibronectin and collagen I deposition several-fold also at concentrations with negligible FVO (<1% v/v). In a cell-free system, incubation of culture media supplemented with fetal bovine serum (FBS), purified fibronectin or collagen I with DxS led to a co-deposition of respective components, exhibiting a similar granular pattern as observed in cell culture. Aggregation of FBS components, fibronectin or collagen I with DxS was confirmed by dynamic light scattering, where an increase in hydrodynamic radius in the respective mixtures was observed. FBS- and fibronectin aggregates could be dissociated with increasing salt concentrations, indicating electrostatic forces to be responsible for the aggregation. Conversely, collagen I-DxS aggregates increased in size with increasing ion concentration, likely caused by charge screening of collagen I, which is net negatively charged at neutral pH, thus permitting weaker intermolecular interactions to occur. The incorporation of DxS into the ECM resulted in altered ECM topography and stiffness. DxS-supplemented cultures exhibited potentiated bioactivity, such as enhanced adipogenic and especially osteogenic differentiation under inductive conditions. We propose an alternative mechanism by which DxS drives ECM deposition via aggregation, and in an independent manner from MMC. A deeper understanding of the underlying mechanism will enable optimized engineering approaches for ECM-rich tissue constructs.
Acceptance Date01/01/2020
All Author(s) ListAssunção M, Wong CW, Richardson JJ, Tsang R, Beyer S, Raghunath M, Blocki A
Journal nameMaterials Science and Engineering: C
Year2020
Month1
Volume Number106
PublisherElsevier
Article number110280
ISSN0928-4931
eISSN1873-0191
LanguagesEnglish-United States
KeywordsDextran sulfate, Extracellular matrix deposition, Macromolecular crowding, Mesenchymal stromal cells, Microenvironment, Tissue engineering

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