POLARIZATION OF CELL LOCOMOTION IN VITRO.

Abstract

Cell locomotion is commonly referred to under such descriptive terms as chemotaxis, galvanotaxis, phototaxis, or thigmotaxis, without identification of the underlying mechanisms. This paper contributes one analytical result. The oriented displacement of a cell relative to its environment is due either to passive convection (e.g., by liquid flow or electrophoresis) or to active locomotion. The latter is biologically more relevant but analytically less well understood. As summarized in an earlier paperl1 it has three distinct and separable aspects relating, respectively, to the motive force, the pathway, and the direction along the pathway. The motive force is provided by metabolic energy, which enables the cell to expand its surface. Contact with a planar or fibrous structure restricts surface expansion to disk or spindle-shape, hence functions as pathway or track (contact guidance, Weiss2). Applied to a linear track, a bipolar spindle cell is still free to move in two opposite directions. In a statistically isotropic environment, a bipolar cell with statistically equivalent poles would therefore remain stationary, shuttling about dead center in accordance with random variations at its two motile tips. To yield directional displacement, this random variation must be overlaid by a persistent polar asymmetry letting one pole advance more actively than the other. With Child,3 one would look for the source of this asymmetry in the cellular environment. The egg of the seaweed, Fucus, can be polarized by external gradients of electric potential, pH, or light.4 If environmental asymmetries were to have similarly polarizing effects on cell locomotion, these could serve as clues to the mechanism underlying the particular taxis. We therefore undertook to test the locomotor behavior of single cells in culture subject to pH gradients and to electric potential gradients, reasoning as follows: The motility of the free margin of a cell varies locally with the state of its surface, which in turn is a function of the metabolic and physicochemical conditions in the particular cytoplasmic sector. Recent experiments in this laboratory5 had revealed that the physicochemical state of an isolated cultured cell changes drastically if the pH of the medium is raised or lowered from its normal level (at 7.4). Above pH 8, the cell contracts vigorously so that a spread-out cell withdraws its pseudopodia and may even detach itself from the substratum; whereas near pH 6 and below, the cell becomes gradually immobilized, as all motion in the interior, signalled by granular or mitotic movements, and of the surface, signalled by the waving of the free border, comes to a standstill in whatever the momentary configuration of the cell may have been. Both of these pH effects are fully reversible, at least within a few hours, upon return to normal medium. The uniformity of the medium in these experiments has left it undecided whether the cell reacts to the pH change as a whole or locally. Could a limited sector of the circumference of a cell be made to contract or be paralyzed locally if that part of its surface were exposed to a pH value higher or lower than the rest? pH Gradients.-Technique: We used cells taken from a stock culture of human