BME Seminar: PhD Students: "Cyclic Stretch Inhibits Cell Invasion and Migration In 3D Scaffolds " Rozanne Mungai & “Measuring Cell Mechanical Anisotropy Using a Toroidal Indentation Probe” Juanyong Li

"Cyclic Stretch Inhibits Cell Invasion and Migration In 3D Scaffolds" -Rozanne Mungai, PhD Student

Cell invasion and migration are fundamental cellular behaviors that drive biological events including morphogenesis, wound healing, cancer metastasis, and infiltration of engineered extracellular matrices (ECM). While cells are known to migrate in response to chemical and physical cues, little is known about the role of dynamic stretch on cell invasion into tissue despite the prevalence of dynamic loading in many organs. The goal of this study is to determine the effect of cyclic stretch on cellular invasion and migration into three-dimensional (3D) ECM. We hypothesize that 10% uniaxial cyclic stretch will reduce cell invasion compared to static culture and that the effect will be most pronounced along the direction of stretch. We utilize a common in vitro cell invasion model involving cell-spheroids embedded in a collagen hydrogel and extend the model to apply 10% cyclic stretch at 1Hz. We couple this model with a custom MATLAB program that saves the individual locations of invaded cell nuclei within captured images and analyze the extent of invasion with novel integrative metrics. We observe that cyclic stretch reduces the extent of invasion compared to static conditions for three mesenchymal cell types (valvular interstitial cells, dermal fibroblasts and smooth muscle cells), yet the reduction is not dependent on the direction of stretch. The cell types had varying degrees of response to stretch with the valvular interstitial cells showing the largest reduction in invasion reduction with stretch. This work has the potential to inform how tissues exposed to cyclic stretch can be more or less susceptible to cell invasion with possible applications in wound healing and the repopulation of decellularized cardiac tissues.

“Measuring Cell Mechanical Anisotropy Using a Toroidal Indentation Probe” -Juanyong Li, PhD Student

Accurate measurement of the stiffness of tissues and cells is critically important in biomechanics and mechanobiology. While biological tissues and cells are generally mechanically anisotropic, experimental measurement of their mechanical anisotropy is hindered by technical difficulties, especially in microscale. Conventional indentation tests, as the gold standard method in measuring stiffness of micro tissues and cells, do not give information related to direction-dependent stiffness owing to the axisymmetric geometry of the probe tip and need to assume mechanical isotropy. This oversimplification may lead to biased interpretation when assessing the mechanical properties and cues. We aimed to develop an indentation method that is able to characterize mechanical anisotropy in small biological materials in a rapid, low-cost, and accessible approach. By using two-photon polymerization (2PP), we 3D-printed micron-size probe tips of a toroidal shape and mounted the printed tip to a commercially available nano-indenter probe. Using this probe, we indented porcine aortic valvular interstitial cells in the direction across and perpendicular to the direction of the long axis of the cell. The indentation curve was fitted to the classic elliptical Hertzian contact model to extract the modulus. A higher modulus was recorded in the indentation across the cells compared to the indentation along the cells. This result indicates the toroidal indenter probe has the ability to measure the mechanical anisotropy in cells. In the future, we plan to derive an analytical model of contact between the toroidal probes and transversely isotropic materials to directly extract anisotropic material parameters. We expect this method can provide broad researchers in biomechanics and mechanobiology with a rapid, low cost, yet robust tool to measure the mechanical anisotropy of micro tissues and cells.

For a zoom link, please email jnorton@wpi.edu or kharrison@wpi.edu