Engineering Polymeric Materials to Study Cancer Dynamics

Cell-induced matrix remodeling is a hallmark of both disease and regeneration. My lab develops biomaterials and matrix characterization methods to study these dynamic cell-matrix interactions.

In designing our biomaterials, we employ protein engineering methods with simple polymer physics models to create biomimetic extracellular matrices for culture of patient-derived organoids. These materials have allowed us to identify matrix stiffness as a previously unknown modulator of chemo-resistance in pancreatic adenocarcinoma (PDAC). Intriguingly, this cellular behavior was reversible upon modulation of the matrix stiffness, suggesting that this may be an ideal pathway for future drug targeting.

In a complementary project, we have developed a micro-rheology strategy that uses dynamic light scattering to characterize the mechanical properties of dynamic materials over time. We have used this method to measure the changes in matrix stiffness in cultures of breast cancer cells.

Interestingly, we discovered that the cells stiffen the matrix at short time-scales, while simultaneously fluidizing the matrix at long time-scales. This seemingly paradoxical stiffening and fluidization are both required for cell invasion within our culture models. Our results suggest a mechanism whereby breast cancer cells reconcile the seemingly contradictory requirements for both tension and malleability in the matrix by differential alteration of matrix mechanics across different time-scales.

Speaker: Sarah Heilshorn, Stanford University