Extracellular matrix plasticity as a driver of cell spreading
Extracellular matrix plasticity as a driver of cell spreading
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DOI：
10.1073/pnas.2008801117
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发表时间：
2020-10-20
影响因子：
11.1
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Grolman, Joshua M.;Weinand, Philipp;Mooney, David J.
哺乳动物细胞形态与粘附底物的粘弹性有关，这在伤口修复和胚胎发育等生物过程中尤为重要，其中细胞的扩散和迁移至关重要。塑性变形、降解和应力松弛在用于探索这些效应的生物材料系统中通常是耦合的，因此不清楚是哪个变量驱动细胞行为。在这里，我们提出了一种不可降解的聚合物结构，具体解耦不可逆蠕变从应力松弛和模量。我们证明，网络可塑性通过依赖于细胞内在力量的双相关系独立控制间充质干细胞的扩散，这种关系可以通过抑制肌动球蛋白收缩性而改变。动力学蒙特卡罗模拟还显示，作为细胞外基质（ECM）可塑性的函数，与实验细胞扩散数据有很强的相关性。此外，可塑性调节许多ECM粘附和重塑基因。总之，这些发现证实了基质可塑性在干细胞生物物理学中的关键作用，我们预计这将对生物材料的设计产生影响，以增强干细胞的治疗应用。
Mammalian cell morphology has been linked to the viscoelastic properties of the adhesion substrate, which is particularly relevant in biological processes such as wound repair and embryonic development where cell spreading and migration are critical. Plastic deformation, degradation, and relaxation of stress are typically coupled in biomaterial systems used to explore these effects, making it unclear which variable drives cell behavior. Here we present a nondegradable polymer architecture that specifically decouples irreversible creep from stress relaxation and modulus. We demonstrate that network plasticity independently controls mesenchymal stem cell spreading through a biphasic relationship dependent on cell-intrinsic forces, and this relationship can be shifted by inhibiting actomyosin contractility. Kinetic Monte Carlo simulations also show strong correlation with experimental cell spreading data as a function of the extracellular matrix (ECM) plasticity. Furthermore, plasticity regulates many ECM adhesion and remodeling genes. Altogether, these findings confirm a key role for matrix plasticity in stem cell biophysics, and we anticipate this will have ramifications in the design of biomaterials to enhance therapeutic applications of stem cells.