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Ph.D. 2002, The George Washington University

Research Areas: Biomedical Engineering, biomaterials, surface science, cell/surface and protein/surface interactions, "smart" surfaces

Brief Description of Research:
 Why does exposure to intense ultraviolet light raise the risk of skin damage and cancer? What causes some medical implants to be readily incorporated into patients, while others are rejected-causing inflammation and scarring?

It may be that the identity and/or state (i.e., native vs. denatured) of the proteins in the extracellular matrix (ECM) extruded by cells provide vital clues to how surfaces affect the viability of cells cultured atop them. Because such differences reflect chemical changes in the protein molecule, they should be evident from chemical detection techniques.

However, the analysis of ECM proteins presents a difficult challenge: the ECM must first be dissociated from the cells to which they are adhered. Usually, the removal of cells cultured on culture surfaces requires harsh enzymatic or mechanical methods which have deleterious effects on the morphological appearance, behavior and chemical makeup of the cells they are harvesting. Such dramatic effects on the cells harvested must be concurrent with damage to the ECM underlying the cells, as well.

We are currently investigating poly(N-isopropyl acrylamide) (pNIPAM) treated surfaces as alternative cell culture surfaces for this very purpose. At normal cell culture temperatures (37°C), cells respond to a pNIPAM-coated surface similarly to those cultured on TCPS. Upon being cooled to room temperature, cells cultured on pNIPAM spontaneously detach as a contiguous sheet. Of special note is that the cells are recovered as intact sheets that retain their function upon transfer to another growth surface, possibly due to the concurrent detachment of an ECM protein. (See Figure 1)


 

 

The unifying goal of our research is to take advantage of the unique thermoresponsive properties of pNIPAM to obtain unperturbed cells, as well as their associated ECM. In this way, we hope to be able to understand the extracellular matrix at a fundamental level by employing all of the techniques available for its study. In the future, such studies will allow us to design novel tissue engineering constructs. In this way, we will be able to study cell/surface behavior from the molecular and cellular levels to the tissue level.

Figure 1. Low-temperature liftoff of a confluent cell sheet allows for direct observation of the apical surface of cell sheets (a), the basal surface of cell sheets with any adhered ECM (b), and the ECM remaining at the culture substrate surface (c).

Laboratory Information

Representative Publications:
Canavan, H.E.; Cheng, X.; Graham, D.J.; Ratner, B.D.; and Castner, D.G., "Cell Sheet Detachment Affects the Extracellular Matrix: A Surface Science Study Comparing Thermal Lift-off, Enzymatic and Mechanical Methods," Journal of Biomedical Materials Research, 75A (1), 1-13 (2005).

Canavan, H.E.; Cheng, X.; Graham, D.J.; Ratner, B.D.; and Castner, D.G., "Surface Characterization of the Extracellular Matrix upon Cell Detachment from a Thermoresponsive Polymer," cover article of Langmuir, 21 (5), 1949-1955 (2005).