Skip to main content
2024 BMES Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Biomechanics

Biomechanics - Poster Session E

Poster P17 - Matrix stress-relaxation regulates neural progenitor-stem cell stemness maintenance and differentiation

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Neural progenitor-stem cells (NPSCs) differentiate into neurons, astrocytes, and oligodendrocytes that populate central nervous system such as brain tissues that are viscoelastic, exhibiting stress-relaxation. Our understanding on NPSCs in such stress-relaxing environment is limited, particularly in stemness maintenance and differentiation. Here, we utilize hydrogels with tunable stiffness and stress relaxation for 3D culture of NPSCs to report that matrix stress-relaxation is important in regulating NPSC stemness and their differentiation into neurons, astrocytes, and oligodendrocytes. We also show that NPSCs’ response to matrix stress-relaxation is mediated by integrin interaction, actomyosin contractility, actin polymerization and the mechanosensitive ion channel Piezo1. These findings emphasize that 3D matrix stress-relaxation functions as a critical mechanical cue in NPSC stemness and differentiation into various lineages through multiple mechanotransduction mechanisms.

Materials and

Methods:  In this work, by using alginate hydrogels with tunable stress-relaxation decoupled from stiffness, we investigated SVZ-derived NPSC stemness maintenance within different stress-relaxing environment. Specifically, we studied the expression of in vivo NPSC marker, RC2. Also, we studied how matrix stress-relaxation influences differentiation outcomes of 3D encapsulated NPSCs towards its progenies, including astrocytes, oligodendrocytes, and neurons. We investigated the role of stress-relaxation in the competition of differentiation into astrocyte and neuronal lineages. We further studied the mechanism of NPSC differentiation regulation by stress-relaxation, including integrin interaction, actomyosin contractility, actin polymerization and a mechanosensitive ion channel Piezo1.

Results, Conclusions, and Discussions: In this work, modulation of NPSC maintenance and differentiation towards neurons, astrocytes, and oligodendrocytes were demonstrated by adjusting 3D environment stress-relaxation properties of NPSCs. NPSCs expressed radial-glial markers upon encapsulation in 3D environment compared to traditional 2D tissue plate culture. Neuron differentiation, astrocyte differentiation, and oligodendrocyte differentiation was enhanced with faster stress-relaxing environment, while stiffness within the tested range had weak or no influence on differentiation outcome. Mixed neuron-astrocyte differentiation cues showed enhanced neuron differentiation with faster matrix stress-relaxation. In mixed differentiation model, integrin interaction, actomyosin contractility, actin polymerization, and Piezo1 activity was shown to be important in regulating neuron differentiation response of NPSCs in fast stress-relaxing environment. This demonstrates these mechanotransduction pathways are involved in sensing stress-relaxing extracellular environments of NPSC regulating differentiation outcome. It is also important to highlight that depending on the differentiation factors the effect of some mechanotransduction pathways differ. These findings provide a new perspective for understanding development and regeneration of CNS tissues, and can be utilized to further harness neural progenies of choice in engineering therapeutic applications.

Acknowledgements (Optional):