Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Friday Speaker Abstracts

Mechanical Signalling in Embryonic Stem Cell Self-renewal and Differentiation Kevin Chalut . University of Cambridge, Cambridge, CAMBS, United Kingdom. Stem cell culture has been characterised using soluble signals on tissue culture plastic, providing a biochemical foundation for self-renewal and differentiation. Nonetheless, most previous stem cell research has overlooked the role of the extracellular matrix (ECM) and mechanical signalling, despite increasing evidence that they both mediate self-renewal and differentiation. To investigate the role of ECM and mechanical signalling, we have developed a novel hydrogel protocol that can be mechanically tuned, ranging from embryo stiffness to skeletal stiffness, while maintaining control of ECM density. We can now present any combination of ECM molecules to cells with independent control over matrix density and stiffness. With our hydrogels, we have explored mechanical and ECM signaling in both pluripotent stem cells and oligodendrocyte progenitor cells (OPCs). We have shown, in both mouse and human, that we can maintain optimal naïve pluripotency using soft substrates with high fibronectin density, while forcing heterogeneity and differentiation on stiff substrates. We have also shown that we can reverse the loss of function associated with ageing and neurodegeneration in OPCs using soft substrates with high laminin density. We will present a number of functional studies to support these conclusions, and I hope to present sequencing data revealing a quantitative analysis of how stiffness drives stem cell identity (samples from both projects are currently being sequenced). Using our hydrogel technology, we have also shown there to be significant actuation of Erk and Stat3 signalling, which are important pathways for self-renewal and differentiation, with mechanical stiffness independent of ECM composition and density. Ultimately, I will advance the hypothesis that mechanical sensing acts as a switch to modulate growth factor signaling to support either self-renewal or differentiation in stem cells.

Nuclear Mechano-genomics and Disease Diagnosis G.V. Shivashankar Mechanobiology Institute, National University of Singapore, Singapore No Abstract

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