Low pH value of pericellular medium as a factor limiting cell proliferation in dense cultures.

An attempt was made to determine the role of metabolic acidification of pericellular medium in regulating cell proliferation. A method of measuring the pH of pericellular medium at a distance exceeding a Debye radius of 5-10 A from the cell surface (pHp) was developed. The values of pHp and pH measured in the medium at a distance of greater than 1 cm from cells (pHm) were found to differ, depending on the cell population density. At a density of at least 7 X 10(5) cells/cm2 (maximum saturation density) and at pHm 7.4-7.6, pHp reached a value of approximately 6.5. It was found that pHm 6.5 was unfavorable for cell proliferation in sparse cultures, where pHm and pHp were equal. Based on these findings, low pHp as revealed in the present work using dense cultures at optimal pHm can be considered to be a limiting factor for cell multiplication.