Dynamic Soft Materials for Deconstructing ‘Matrix Structure—Cell Function’ Relationships

Dynamic soft materials for deconstructing
�matrix structure�cell function� relationships

�

Amr A. Abdeen, Kristopher A. Kilian

Department of Materials Science and
Engineering, Department of Bioengineering, Micro and Nanotechnology Laboratory,
Institute for Genomic Biology

�

The
extracellular matrix surrounding cells in tissue is a dynamic composite
material, where the presentation of biophysical and biochemical information
directs functional bioactivities. Here I will discuss how engineered model
systems can be leveraged to explore how cells receive and integrate signals to adopt
specific bioactivities. We have discovered how engineering actomyosin
contractility in single mesenchymal stem cells can normalize the population and
�activate� a medicinal state. Variations in subcellular curvature will guide
focal adhesion, cytoskeletal organization, and the regulation of distinct
epigenetic marks to orchestrate a medicinal secretome. Within two days,
activated cells show elevated expression of pericyte markers, and will
recapitulate functional pericyte activity through enhanced association with
endothelial cell tubules in co-culture. Enhanced angiogenesis is demonstrated
in vivo using micropatterned hydrogels applied to a chick chorioallantoic
membrane assay. I will also demonstrate a dynamic magnetically-tunable hydrogel
that can reversibly stiffen in response to permanent magnets to modulate stem
cell differentiation and pro-angiogenic activity. MSCs are believed to undergo
a temporary switch in vivo to an activated state in response to injury; thus we
propose engineering actomyosin contractility after isolation can similarly
activate MSCs, which may serve as a general approach to prime a medicinal
phenotype for improved efficacy of cell-based therapies.

�