Fig. 1.
Mechanical plasticity of interpenetrating networks of alginate and reconstituted basement membrane matrix (IPNs) can be independently tuned. a Schematic depicting invasion of basement membranes (green) during invasion and metastasis. b Schematic depicting the indentation tests performed on human mammary tumor tissue, and the corresponding force vs. indentation depth curves (green arrow—permanently retained indentation; red arrow—drop in peak force during second indentation; dotted line—25% of initial peak force). Subplot shows indentation test profile. c Before and after images of an indented mammary tumor sample. Indentation region outlined by dotted circle, and discolored tissue regions indicated by black arrows. Scale bar is 1 mm. d Indentation plasticity measurements of human tumor (two specimens from a tumor sample) and mouse tumor specimens (one sample each from four separate mice). e Schematic of approach to tuning matrix plasticity in IPNs of alginate (blue) and reconstituted basement membrane (rBM) matrix (green). f, g Young’s moduli (f) and loss tangent (g) of the different IPN formulations. The differences in loss tangent indicated are significantly different (**P < 0.01, ****P < 0.0001, ANOVA; ns not significant), as is the increasing loss tangent across this series of IPNs (####P < 0.0001, Spearman’s rank correlation). h Schematic depicting the elastic, viscoelastic, and plastic (permanent) portions of a material response in a creep and recovery test. i Representative creep and recovery tests of IPNs. j Permanent strain of IPNs, polyacrylamide gels (PA), and silly putty from creep and recovery tests. Statistically significant differences are indicated (**P < 0.01, ****P < 0.0001, ANOVA), plasticity across the IPNs (####P < 0.0001, Spearman’s rank correlation). k Permanent strain of HP IPN, alginate hydrogel, rBM matrix, and col-1 gels from creep–recovery tests. Statistically significant differences compared to HP IPN are indicated (****P < 0.0001, ANOVA). In f–k, bars indicate means and error bars indicate 95% confidence interval of the indicated biological replicates. l Permanent strain and loss tangent are correlated in the IPNs (R2 = 0.7953). m Partition coefficients for PEGylated gold nanoparticles of the indicated size encapsulated in IPNs for 4 days