A synthetic hydrogel for the high-throughput study of cell-ECM interactions.
It remains extremely challenging to dissect the cooperative influence of multiple extracellular matrix (ECM) parameters on cell behaviour. This stems in part from a lack of easily deployable strategies for the combinatorial variation of matrix biochemical and biophysical properties. Here we describe a simple, high-throughput platform based on light-modulated hyaluronic acid hydrogels that enables imposition of mutually independent and spatially continuous gradients of ligand density and substrate stiffness. We validate this system by showing that it can support mechanosensitive differentiation of mesenchymal stem cells. We also use it to show that the oncogenic microRNA, miR18a, is nonlinearly regulated by matrix stiffness and fibronectin density in glioma cells. The parallelization of experiments enabled by this platform allows condensation of studies that would normally require hundreds of independent hydrogels to a single substrate. This system is a highly accessible, high-throughput technique to study the combinatorial variation of biophysical and biochemical signals in a single experimental paradigm.
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Andrew D
AD
Rape
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Mikhail
M
Zibinsky
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Niren
N
Murthy
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Sanjay
S
Kumar
D000273:Adipose Tissue / Q000166:cytology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008689:Methacrylates / Q000737:chemistry*; D035683:MicroRNAs / Q000235:genetics*; D008858:Microscopy, Phase-Contrast; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005353:Fibronectins; D020100:Hydrogels; C522576:MIRN18A microRNA, human; D008689:Methacrylates; D035683:MicroRNAs; D006820:Hyaluronic Acid