New evidence that growth in 3T3 cell cultures is a diffusion-limited process

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Abstract
When a confluent culture of 3T3 cells is wounded, new growth occurs at the wound margins. This indicates that the suppression of growth in the intact confluent sheet is under local control, a phenomenon known as ‘topoinhibition’1, and it has been suggested that intercellular contact is responsible. An alternative explanation for topoinhibition is possible, however, namely that a soluble factor necessary for growth is locally depleted from the medium by cells so that each cell in a confluent sheet normally receives an insufficient supply and its growth is inhibited2–5. Here we show that the pattern of release from topoinhibition in a wounded culture can be distorted simply by inducing a gentle laminar flow of medium across the wound. Growth remains suppressed at the upstream margin of the wound despite the reduced level of intercellular contact at wound edges. We conclude that the signal for topoinhibition is carried by the flow as would be predicted if it were the local depletion of growth factor.