The membrane theory and other views for solute permeability, distribution, and transport in living cells.

Abstract

THE MEMBRANE THEORY AND OTHER VIEWS FOR SOLUTE PERMEABILITY, DISTRIBUTION, AND TRANSPORT IN LIVING CELLS GILBERT N. LING* Investigations on the physiology of living cells have so far largely followed the direction ofa specific theory, the membrane theory. A review of the history reveals how in its early stage of development this theory evolved side-by-side with the investigations of the physical phenomenon ofosmosis. Osmosis arises from the property ofa specific type of membrane, the semipermeable membrane [i]. The earliest semipermeable membranes used in osmosis studies were animal and plant membranes . However, the phenomena of membranes allowing water to go through, but not water-soluble solutes such as alcohols and sugars, are not limited to tissues of living or once-living organisms, but are also shown by inanimate systems. With interest both in osmosis and in the behavior ofliving cells, Pfeffer [2] was impressed by the similarity ofthe behavior of living cells and that of a sac containing certain impermeant solutes and a semipermeable membrane. He suggested, and thus founded, the membrane theory—i.e., that it is the plasma membrane of the cell which determines the composition ofthe intracellular contents and not the cytoplasm, even though the postulated plasma membrane was not yet demonstrable with the best microscope then available, and even though all the animal and plant membranes used in osmotic work consisted of entire cells, the bulk ofwhich were obviously made up ofthe cytoplasm. One ofthe major contributions ofM. Traube [3] was his discovery of the artificial semipermeable membrane made ofcopper ferrocyanide gel; * Department of Molecular Biology in the Department of Neurology, Division of Medicine, Pennsylvania Hospital, Philadelphia, Pennsylvania. This research was supported by research grants from the Office of Naval Research (1-2060-66) and from the National Institutes of Health (gm11422 -01 and GM K3-19, 032). 87 within my knowledge, nobody has yet found a better artificial semipermeable membrane [4]. The copper ferrocyanide precipitation membrane is not only nearly ideal in its impermeability toward non-electrolytes, such as sugar, it is also impermeable toward both anions and cations. Perhaps cellular physiology could have taken a different course (see below) if copper ferrocyanide had received continued and intensive attention in the year following the discovery and early studies. As it was, most cell physiologists were more attracted to a different model ofthe cell membrane , the lipoid layer. I.The Lipoid Membrane Theory At the turn ofthe twentieth century, Overton studied the permeabilities of many substances into a variety of plant and animal cells [5]. He discovered a parallelism between the permeating power ofa substance and its relative solubility in lipoid solvents. He proposed the lipoid theory, according to which the plasma membrane ofliving cells represented a continuous lipoid layer. The substances whose permeabilities follow this relation to lipoid solubilities were certain non-electrolytes, or, more correctly , ?-bonding substances that do not carry net charges. Other non-electrolytes (e.g., sugars), electrolytes, and Zwitterions (e.g., amino acids) do not follow this rule since they are lipoid-insoluble but do enter the cells. Overton explainedthisapparent anomaly to his rule by proposing a totally different mechanism—"adenoid" (or secretive) activity which transported these specific solutes across the postulated membranes in an undefined manner [6]. In setting out his lipoid theory, Overton had separated certain non-electrolytes, such as amides and simple alcohols, into one category and polyhydric alcohols, amino acids, and electrolytes into another. This artificially introduced dichotomy was to persist in subsequent investigations for a long time to come. II.The Sieve-Membrane Theory Overton postulated that all electrolytes, amino acids, and sugars enter the cells by adenoid activity (active transport). The majority ofworkers dealing with water and electrolytes movements did not accept the concept ofa continuous lipoid membrane; they thought that the plasma membrane had aqueous channels [7]. Others postulated that these channels had a critical diameter which permitted small ions to enter but did not permit Gilbert N. Ling · Membrane Theory and Other Views Perspectives in Biology and Medicine · Autumn 1963 the larger ones to enter [8]. The sieve concept reached the height ofits development with the publication of the theory of Boyle and Conway. These authors offered a unified pore-size interpretation...