Sarah Heilshorn, Stanford University
Adaptable, Protein-Engineered Hydrogels for Organoid Culture
Written by Jessalyn Low
Three-dimensional culture matrices are essential to support organoid formation. Commonly used matrices like Matrigel, however, have limited translational potential as it is animal-derived and exhibit low batch-to-batch similarity. In this talk, Heilshorn reports the development of a novel hyaluronan elastin-like protein (HELP) matrix which was demonstrated to support the formation, passaging, and differentiation of patient-derived intestinal organoids. Properties of the HELP matrix such as matrix stiffness, stress relaxation rate, and density of cell-receptor ligands are tunable and can be optimized by studying the interactions between the cells and polymers. In line with this, it is also essential that techniques are developed to probe the cell-matrix interactions. To do so, Heilshorn presents the development of a broadband dynamic light scattering microrheology (DLSµR) technique. DLSµR is advantageous as it can probe stiffness over a wide range of values, and also achieve data over an extended timescale, which allows for a wide range of cellular processes to be studied. Using DLSµR, it was demonstrated that it could capture cell-induced changes in matrix mechanics and allow estimation of dynamic matrix mechanics, highlighting its use in studying living soft matter changes over time.