Meta-analysis and experimental re-evaluation of the Boyle van ‘t Hoff relation with osmoregulation modelled by linear elastic principles and ion-osmolyte leakage

Abstract

In this study we challenge the paradigm of using the Boyle van 't Hoff (BvH) relation to relate cell size as a linear function of inverse extracellular osmotic pressure for short time periods (~5 to 30 mins). We present alternative models that account for mechanical resistance (turgor model) and ion osmolyte leakage (leak model), which is not accounted for by the BvH relation. To test the BvH relation and the alternative models, we conducted a meta-analysis of published BvH datasets, as well as new experiments using a HepG2 cell line. Our meta analysis showed that the BvH relation may be assumed of the hypertonic region but cannot be assumed a priori over the hyper and hypotonic region. Both alternative models perform better than the BvH relation but are nearly indistinguishable when plotted. The return to isotonic conditions plot indicated neither alternative model accurate predicts return volumes for HepG2 cells. However, a combined turgor leak model accurately predicts both the BvH plot and the return to isotonic conditions plot. Moreover, this turgor leak model provides a facile method to estimate the membrane cortex Young's modulus and the cell membrane permeability to intracellular ions/osmolytes during periods of osmotic challenge, and predicts a novel passive method of volume regulation without the need for ion pumps.

On the involvement of cell volume regulation mechanisms in post-hypertonic lysis and slow-freezing injury of human erythrocytes and its broader cryobiological significance

“…The models are developing, as evidenced by recent efforts to account for deviations in the osmotic behavior of different cells [29][30][31] by incorporating the possibility of ion movements into the mathematical models describing the cell behavior. [32][33][34] It should be emphasized that although the impermeability assumption is often adequate, it is inconsistent with the current state of physiological knowledge, which perceives the plasma membrane as permeable to ions such as Na + , K + , and Cl -. A typical cell (including human RBC) is characterized by low intracellular content of sodium ions and high content of potassium ions and by negative electric membrane potential at steady-state conditions.…”