Role of Cell-Mediated Enzymatic Degradation and Cytoskeletal Tension on Dynamic Changes in the Rheology of the Pericellular Region Prior to Human Mesenchymal Stem Cell Motility,ACS Biomaterials Science & Engineering

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Role of Cell-Mediated Enzymatic Degradation and Cytoskeletal Tension on Dynamic Changes in the Rheology of the Pericellular Region Prior to Human Mesenchymal Stem Cell Motility
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-01-19 00:00:00 , DOI: 10.1021/acsbiomaterials.7b01005
Maryam Daviran ₁ , Hugo S. Caram ₁ , Kelly M. Schultz ₁

Affiliation

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.

中文翻译：

细胞介导的酶降解和细胞骨架张力对人间充质干细胞运动之前周细胞流变学动态变化的作用

将人间充质干细胞（hMSCs）封装在合成基质金属蛋白酶（MMP）可降解的聚（乙二醇）肽水凝胶中，以使用多种粒子跟踪微流变技术表征细胞介导的周缘区域降解。水凝胶支架被细胞分泌的酶和细胞骨架张力降解。我们确定细胞分泌的酶促降解是细胞周围区域变化的主要因素，而细胞骨架张力起着最小的作用。未经处理的和肌球蛋白II抑制的hMSC的测量降解曲线在细胞周围具有最高的交联密度。我们假设细胞还分泌金属蛋白酶组织抑制剂（TIMPs）来抑制MMP，MMPs允许细胞在运动之前扩散和附着。

更新日期：2018-01-19

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