EFFECT OF EXTRACELLULAR-MATRIX TOPOLOGY ON CELL STRUCTURE, FUNCTION, AND PHYSIOLOGICAL RESPONSIVENESS - HEPATOCYTES CULTURED IN A SANDWICH CONFIGURATION

Extracellular matrix (ECM) geometry is an important modulator of cell polarity and function, For example, 3-dimensional matrices often more effectively induce differentiated cell function than traditional 2-dim ensional substrates, The effect of ECM topology can be investigated in a controlled fashion using a technique whereby cells cultured on a si ngle surface are overlaid with a second layer of ECM, thereby creating a ''sandwich'' configuration, Confluent monolayers of epithelial or e ndothelial cells overlaid in this fashion often reorganize into struct ures that are reminiscent of their native tissue, In the case of hepat ocytes, the overlay causes a dramatic reorganization of the cytoskelet on, adoption of in vivo-like morphology and polarity, and expression o f a wide array of liver-specific functions. In this short review, we u se the sandwiched hepatocyte culture system to illustrate the effect o f ECM geometry on cellular function, Pertinent studies are summarized in the context of defining the parallels, strengths, and Limitations o f this culture system as an in vitro model to study the physiology and morphogenesis of liver tissue, We also explore some of its a potentia l uses as a model to study liver pharmacology and toxicology, and for the development of Liver preservation techniques and liver-assist devi ces.