机械转化
干细胞
细胞生物学
材料科学
细胞分化
细胞
刚度
基质(化学分析)
纳米技术
生物
复合材料
遗传学
生物化学
基因
作者
Anna L. Kersey,Daniel Y. Cheng,Kaivalya A. Deo,Christina R. Dubell,Ting‐Ching Wang,Manish K. Jaiswal,Min Hee Kim,Aparna Murali,Sarah E. Hargett,Sumana Mallick,Tanmay P. Lele,Irtisha Singh,Akhilesh K. Gaharwar
出处
期刊:Biomaterials
[Elsevier]
日期:2024-01-01
卷期号:: 122473-122473
标识
DOI:10.1016/j.biomaterials.2024.122473
摘要
Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cell behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular response. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell–ECM mechanotransduction in 3D.
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