The concepts of membrane flow and membrane vesiculation as mechanisms for active transport and ion pumping.

TLDR: The hypothesis that membrane flow may be an important part of a type of active transport mechanism carrying particles, including ions, along, within, into, and out of cells is introduced.

Abstract: Dr. Palade has shown that in many cells the cell membrane is infolded extensively and that such folds may carry the cell membrane to positions deep in the cell. Moreover, he has shown that such deep folds often appear to lie close to isolated vesicles in the cytoplasm. Dr. Palade has pointed out that such vesicles are often arranged so as to suggest that they might have formed from the pinching off of a recessed tip of such a fold, or that they might represent vesicles destined to coalesce with such a recessed fold. Dr. Palade referred to the classical paper on pinocytosis by Lewis (8). Lewis showed cells in which the cell surface and adjacent cytoplasm were in a state of vigorous activity, with an orderly flow of granules and vesicles from one portion of a cell to another. Similar activity and orderly movements within cells have been demonstrated by Gey, Shapras, and Borysko (6), by Frederic and Ch~vremont (5), and by Blandau, De Marsh, and Ralph (1). Dr. Palade's pictures suggest that in such cells as macrophages, in which pinocytosis and orderly flow of cytoplasmic particles are evident, the cytoplasmic membranes of the endoplasmic reticulum, particularly those components representing membranes folded inwards from the outer cell border, might participate in or even mediate these activities. I would like to introduce the hypothesis that membrane flow may be an important part of a type of active transport mechanism carrying particles, including ions, along, within, into, and out of cells. If membrane is being formed or synthesized in one region, and is being broken down or enzymatically destroyed at another, it would be expected to flow from the membrane source to the membrane sink or site of breakdown. If the source is at the exposed cell surface, as at A and A' in Fig. 1, and the sink is deep in the cell as at B (Fig. 1), the membrane would flow from the surface to a position deep in the recess as indicated by the arrows. A membrane flow in the reverse direction would result from a source at the tip of the recess at B and a sink on the surface at A or A'. Membranes entirely within the cell or entirely on the exposed cell surface or extending through the cell as tunnels or slits could be envisioned as similarly motivated to flow from sources to appropriately placed sinks. The energy required for such kinesis would be provided by oxidative mechanisms in the cell. 99