Inherent Interfacial Mechanical Gradients in 3D Hydrogels Influence Tumor Cell Behaviors

Cells sense and respond to the rigidity of their microenvironment by altering their morphology and migration behavior. To examine this response, hydrogels with a range of moduli or mechanical gradients have been developed. Here, we show that edge effects inherent in hydrogels supported on rigid substrates also influence cell behavior. A Matrigel hydrogel was supported on a rigid glass substrate, an interface which computational techniques revealed to yield relative stiffening close to the rigid substrate support. To explore the influence of these gradients in 3D, hydrogels of varying Matrigel content were synthesized and the morphology, spreading, actin organization, and migration of glioblastoma multiforme (GBM) tumor cells were examined at the lowest (<50 µm) and highest (>500 µm) gel positions. GBMs adopted bipolar morphologies, displayed actin stress fiber formation, and evidenced fast, mesenchymal migration close to the substrate, whereas away from the interface, they adopted more rounded or ellipsoid morphologies, displayed poor actin architecture, and evidenced slow migration with some amoeboid characteristics. Mechanical gradients produced via edge effects could be observed with other hydrogels and substrates and permit observation of responses to multiple mechanical environments in a single hydrogel. Thus, hydrogel-support edge effects could be used to explore mechanosensitivity in a single 3D hydrogel system and should be considered in 3D hydrogel cell culture systems

The dynamics of shrinking and expanding drug-loaded microspheres: A semi-empirical approach

The dynamics of shrinking and expanding drug-loaded microspheres were studied using a diffusion equation in spherical coordinates. A movable boundary condition was incorporated as a convection term in the original model. The resulting convective-diffusive problem was solved using Laplace transform techniques with the Bromwich integral and the residue theorem. Analytical solutions were derived for the general case of shrinking or expanding microspheres and three particular kinetics expressions: linear growth, exponential swelling and exponential shrinking. Simulations show that microspheres with fast-swelling kinetics released their therapeutic cargo at a relatively slow rate in the first two cases. Ninety-nine percent of the medication was delivered at four times the effective time constant. In line with laboratory studies using bovine serum albumin, an increase in the shrinking rate led to a fast release of the medication from its carrier. The method was applied to analyze insulin transport through spherical Ca-alginate beads. A good agreement was noted between predicted and experimental data. The theoretical effective time constant was 114.0 min