Abstract
Cells swell in response a hypoosmotic challenge. By converting osmotic pressure to hydrostatic pressure at the cell membrane via van't Hoff's law, and converting that to tension via Laplace's law one predicts that the cell membrane should stretch and become stiff. We tested this prediction using the atomic force microscopy. During osmotic swelling cells did not become stiff and generally became softer. This result contradicts the assumption of the cell membrane as the constraining element in osmotic stress but is consistent with the cytoskeleton acting as a cross-linked gel. Models of the cells' response to osmotic stress must include energy terms for three-dimensional stresses.