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Cell & Tissue Engineering: Overall Research Theme

Over the last 30 years, the tools of molecular biology and cell biology have provided us with great insights into the mechanisms of cellular function. But how do these cells interact with each other and with their environment to form complex tissues and organs? To address this question, we are developing new tools to study multiple cells types and their extracellular environments in 2D and 3D. In particular, we use techniques in microtechnology to position the cells, and molecular design to tune the cellular interactions with their surroundings; overall, we employ techniques from a number of different fields, including biochemistry, molecular biology, microfabrication, microfluidics, materials chemistry, and cell and tissue biology.

Cell-Cell Communication

Formation of complex tissues depends strongly on the ability of large populations of cells to self-organize. This cellular communication is achieved either through direct interactions (such as gap junctions) or indirect interactions (such as hormones). Using traditional biological methods, it is often difficult to uncouple these two mechanisms. We will take advantage of recent tools in microtechnology to study the mechanisms of intercellular communication within different geometries of simulated physiological systems.

Cell-Environment Interactions

In studies of multiple cell types and the engineering of artificial tissues, it is often desirable to control how individual cells interact with their surroundings (either an extracellular matrix or an artificial material). We will take a first step to addressing this challenge by modulating the affinities of different cell types for different surfaces. Because such interactions are ultimately molecular in nature, we will design small molecules, peptides, and proteins (beyond often-used molecules such as fibronectin and the RGD sequence) to promote desired cell-environment contacts, while disfavoring other potential interactions.

Microenvironment

To understand how cells behave in tissue-like environments, it is important to control the environment itself. The natural environment of cells is the extracellular matrix, dominated by protein fibers (such as collagen) that give proper mechanical strength to the matrix and that promote appropriate internal cellular signalling. We will modify the molecular structures of the protein fibers (thereby changing the mechanical and signalling properties of the extracellular matrix), and probe these effects on cellular behavior.

MEMS Devices for Global Health

Lab-on-a-chip devices have the potential to revolutionize public health by allowing complicated medical testing procedures to be performed on a small microfluidic chip. Thus far, however, they have not been used in developing countries (such as those in sub-Saharan African and southeast Asia) because they have not been low-cost, simple to use, or portable. We are developing new lab-on-a-chip diagnostic devices specifically for use in resource-poor settings such as developing countries.