Molecular traffic through plasma membrane disruptions of cells in vivo

We have recently shown that mechanical forces, experimentally imposed or physiologically generated, transiently disrupt or wound the plasma membranes of epithelial cells of the gut and that cultured endothelial cells similarly wounded mechanically at their plasma membranes release a potent basic fibroblast growth factor-like molecule. Here we show that mechanical forces generated by experimental manipulation (tape stripping and needle puncture), or by animal locomotion, transiently wound the plasma membranes of various cells of skin, allowing otherwise impermeant tracer molecules to enter and become trapped within cell cytoplasm. We estimate that the epidermis of digits from actively locomoting animals is composed of 10.5% (+/- 4.9% S.D.) wounded cells, and that from quiescent animals has 3.7% (+/- 2.5%) wounded cells. Wounded fibroblast, glandular and endothelial cells were also identified in mechanically stressed skin. Cells retaining fluorescein dextran, used as a label for wounding, were observed 24h after the imposition of mechanical force, and wounded cells were generally of normal ultrastructure, indicating that cells in skin can survive membrane wounding. We propose that plasma membrane disruptions are an overlooked but probably common occurrence in cells residing in tissues such as gut and skin that are normally exposed to mechanical stress in vivo, and that such disruptions provide the physical basis in vivo for a previously unrecognized and diffusion-mediated route for molecular traffic directly across the plasma membrane into and out of living cell cytoplasm.