Research

Cell migration occurs for both good and bad reasons in your body. For example, when a wound is generated, many different cell types flock to the wound site to destroy infectious microorganisms and repair the tissue. Alternatively, tumor cells may, for still poorly understood reasons, decide to leave the tumor, invade the surround tissue, and generate metastases at distant sites in the body. There are several ways that cells can move through the body, but many of them involve migrating over or through extracellular matrix (ECM), which is a network of fibrillar proteins, proteoglycans, glycosoaminoglycans, and other molecules. However, most cell migration research has been performed on cells migrating on glass or plastic substrates with very different physical and chemical properties than normal ECM. For example, ECM is typically softer than glass or plastic, and is also three-dimensional, porous, and fibrous. Our research studies how basic components of crawling cell migration—adhesion, protrusion, and polarity—are guided by specific properties of the ECM. We are currently focusing on the role of matrix fiber architecture: how it both guides and is changed by cell migration.

Cells in the body deposit, rearrange, and degrade ECM in many situations, from the early stages of embryogenesis to wound healing in an adult. Since ECM comprises a major portion of most tissues, these processes are highly regulated and precisely orchestrated. They can, however, be subverted by, for example, cancer cells that may alter the ECM structure to enable tumor growth and metastasis. Unfortunately, most bioengineered tissues also tend to disrupt normal ECM structure and function, triggering cells to produce disorganized tissue rather than normal tissue. Current artificial tissue scaffolds do not effectively control the deposition and properties of new matrix and little is known about the requirements for such guidance. We are currently focusing on identifying how specific scaffold properties affect the architecture of cell-generated fibronectin ECM.

Articular cartilage, a dense but flexible connective tissue covering the surface of articulating joints, allows for smooth, frictionless movement while also absorbing the load-bearing forces required in walking. Unfortunately, trauma or disease induces tissue damage leading to chronic cartilage degradation. Tissue engineering strategies using cells and various types of biomaterials have emerged as a promising approach for cartilage repair; however, the scaffold design parameters that guide cartilage cells to heal damaged tissue are still poorly understood.

To understand how chondrocytes generate cartilage tissue and what stimuli promote aberrant tissue formation, it is necessary to visualize cell behavior at high spatial resolution in an environment that mimics natural tissue (whether healthy or damaged) and can be modified to test different properties. However, there are few platforms that allow such investigations. Traditionally, cells are grown on glass or plastic dishes, which permit excellent imaging conditions but do not mimic natural cartilage. Current tissue engineered scaffolds provide a more physiological environment but do not have easily standardized or modifiable properties, and do not allow optimal high-resolution imaging of cells. Our goal is to engineer a cell culture platform that provides a physiological environment with modifiable properties and enables high resolution monitoring of chondrocyte behavior. We will then use this model system to identify how specific properties of the scaffold/ECM environment affect chondrocyte phenotype, in particular cartilage tissue formation.