A Gel-Based Model of Selective Cell Motility Involving Chemotaxis, Haptotaxis and Durotaxis: Implications for Cell Sorting, Diagnostics and Screening

The ability to precisely control cell-loaded material systems is essential for in vitro testing of novel therapeutics poised to advance to clinic. In this report, unique patterns of cell migration by chemotaxis were devised into an in vitro gel-in-gel model for the purpose of obtaining cell response data to potentially therapeutic agonists. The model consisted of co-cultures in a cell-loaded microgel invading an acellular “sorting” gel. Material properties including biophysical and chemical composition of the sorting gel were carefully controlled to guide a desired cell-specific behavior, leading to massive tumor cell invasion by amoeboid migration mechanisms. Optical transparency enabled straightforward and high-throughput measurements of outgrowth response in the presence of either chemical and photo-radiation therapy. Important dosing and drug sensitivity information were obtained with the gel-in-gel model using no more than a light microscope, without further need for arduous genomic or proteomic screening of the tissue samples.