Session A23: Biological Fluid Dynamics: Flows in Tissues

Hydrodynamic investigation of polymeric scaffold degradation for bone regeneration applications

Porous, polymeric scaffolds are being designed for controlled delivery of nutrients that support osseous tissue growth and vascular formation for the treatment of maxillofacial trauma. Premature degradation of these hydrophilic, polyvinyl alcohol (PVA)-based scaffolds can occur due to pulsatile nature of blood flow and mechanical loading. Our hypothesis is that vascular network growth (or neovascularization) emanating from the maxillary artery initiates swelling and erosion of PVA-based scaffolds, and dispersion of released polymers. Scaffold structural properties were determined by tensile testing of PVA structures at different hydration times. Diffusivity of PVA suspensions and their size distribution were measured in a dynamic light scattering instrument. Viscoelastic rheology measurements established the viscosity-averaged molecular weight of the PVA suspensions in deionized water. Scaffold fragmentation was monitored in a flow loop under varying flow pulsatility using MEMS-based pressure catheters and an ultrasonic flow rate sensor. Knowledge gained will facilitate the design of scaffold matrices using biocompatible polymers with tunable degradation characteristics and predictable material release.   

Correlating Tissue-level Elasticity and Surface Tension with Cellular-level Properties and Shape Statistics

Cellular aggregates are well known for their liquid-like, viscoelastic behavior. Upon mechanical compression and relaxation, cells within an aggregate rearrange themselves to minimize system energy. However, quantitative correlations between the aggregate-level properties and the cellular-level properties are largely unclear. In this work, we simulate 2D cellular rearrangement inside an initially circular aggregate upon plate compression using Surface Evolver. Two tissue energy models from previous literatures are implemented. By attributing the volume-associated energy to bulk elasticity and the surface-associated energy to surface tension, we quantitatively correlate the mechanical properties of aggregate with cellular-level properties as well as cell shapes and statistics for each model. The results suggest that under certain conditions, cells on aggregate surface can maintain a much higher energy state than those in the interior, which corroborates our previous experimental work (Yu et al., BpJ 114, 2703-16).   

Extensile motor activity drives coherent flows in a model of interphase chromatin

The 3D spatiotemporal organization of genetic material inside the cell nucleus remains an open question in cellular biology. During the time between two cell divisions, chromatin – the functional form of DNA in cells – fills the nucleus in its uncondensed polymeric form. Recent in-vivo imaging experiments have revealed the existence of coherent motions inside the nucleus, with correlated displacements on the scale of microns and lasting for seconds. To elucidate the mechanisms behind these motions, we develop a novel coarse-grained model where chromatin is represented as a confined flexible chain acted upon by active molecular motors that perform work by exerting dipolar stresses on the system. Numerical simulations of this model account for steric and hydrodynamic interactions as well as internal chain mechanics, and demonstrate the emergence of coherent motions in systems involving extensile dipoles, which are accompanied by large-scale chain reconfigurations and local nematic ordering. Comparisons with experiments show good qualitative agreement and support the hypothesis that long-ranged hydrodynamic couplings between chromatin-associated active motor proteins are responsible for the observed dynamics.