Understanding the material properties of the nanofibers comprising electrospun scaffolds for tissue engineering will elucidate the mechanotransduction of cells seeded onto and attached those scaffolds. The overall mechanical properties of any structure built from fibers depend on 1) the architecture, 2) the properties of the constituent single fibers, and 3) the junctions between fibers. All three must be known to design a structure with predictable mechanical properties. We hypothesize that a basic understanding of the nanolevel mechanical properties of individual electrospun fibers will enable accurate prediction of the overall cellular response and bulk mechanical behavior of electrospun tissue scaffolds.

There is currently a significant clinical need for artificial salivary glands as a therapeutic option for patients suffering from xerostomia. To achieve unidirectional fluid secretion, the epithelial acinar cells must establish and maintain polarity by partitioning the plasma membrane into distinct apical and basolateral membrane surfaces to achieve unidirectional fluid secretion. Establishment and maintenance of epithelial acinar cell polarity has been difficult to achieve in vitro, and yet is critical saliva secretion in an engineered salivary gland. Physical properties of the scaffold provided to epithelial cells will likely influence their ability to differentiate and achieve apical-basal polarity. We have engineered nanofiber matrices using the biocompatible polymer, PLGA (poly-L-lactic-co-glycolic acid) having differing topology and organization and documented the structure of these scaffolds using SEM. We evaluated the effects of several factors on epithelial cell attachment, self-organization, and apico-basal polarity on the scaffolds using confocal microscopy to examine expression and organization of apical tight junction proteins, ZO-1 and claudins, and basal markers, such as integrin α6 and the ECM protein fibronectin. The surface of the nanofiber matrix was functionalized with chemically-linked ligands to further optimize apical-basal polarity. These studies will identify an optimal scaffold for future use in an engineered functional salivary gland construct.

Cells in tissues and organs coordinate their activities with each other, and this communication is mainly mediated by specialized channels, called Gap Junctions. To date, our understanding of specificity of reagents and extracellular stimuli to gap junctions is very limited. Existing techniques for gap junctions assay are tedious and not convenient. We have developed a microfluidic chip that is capable of detecting chemical diffusion across gap junctions, as well as screening reagents for specific gap junction channels.

Metastasis, the spread of cancer cells throughout the body, claims 90% of solid tumor deaths. During metastasis, cancer cells undergo discohesion. An understanding of how to control and strengthen cell adhesion through junction formation could lead to methods for decreasing metastatic tendencies.

Advancements in technologies for assessing biomechanics at the cellular level have led to discoveries in the relationship between mechanics and biology (mechanotransduction) and the investigation of cell mechanics as a biomarker for disease [1]. With the recent development of an integrated optical tweezer with micron resolution particle image velocimetry (436 nm spatial resolution), the opportunity to apply controlled multiaxial stresses to suspended single cells is available [2]. A stress analysis was applied to experimental and theoretical flow velocity gradients of suspended cell-sized polystyrene microspheres in microfluidic environments representing the relevant geometry of non-adhered spherical cells as observed for osteoblasts, chondrocytes, and fibroblasts [3]. That analysis identified a very low level of applied stresses available during creeping laminar flow within straight and cross-junction microfluidic channel arrangements with uniform and extensional flows, respectively. As a followup study, the objective here was to apply a range of normal and shear stress profiles in a two-dimensional, computational analysis and estimate the responding cellular strains.