Cell mechanics and stress: from molecular details to the ‘universal cell reaction’ and hormesis

Abstract

The 'universal cell reaction' (UCR), a coordinated biphasic response to external (noxious and other) stimuli observed in all living cells, was described by Nasonov and his colleagues in the mid-20th century. This work has received no attention from cell biologists in the West, but the UCR merits serious consideration. Although it is non-specific, it is likely to be underpinned by precise mechanisms and, if these mechanisms were characterized and their relationship to the UCR elucidated, then our understanding of the integration of cellular function could be improved. As a step towards identifying such mechanisms, I review some recent advances in understanding cell mechanics and the stress response and I suggest potentially testable hypotheses. There is a particular need for time-course studies of cellular responses to different stimulus doses or intensities. I also suggest a correspondence with hormesis; re-investigation of the UCR using modern biophysical and molecular-biological techniques might throw light on this much-discussed phenomenon.

Elucidating the Mechanism(s) of Hormesis at the Cellular Level: The Universal Cell Response

“…Mechanisms such as those proposed by Szabadi [22] and by Connolly and Lutz [15] may conceivably lead to, or participate in, such a final common pathway. It has been suggested that hormesis at the cell level is a manifestation of, or is identical to, the UCR [31,32] . This is the position adopted in the present article.…”

“…This proposal is corroborated by the fact that lipophilic xenobiotics such as valinomycin bind to a wide range of intracellular proteins [33] and that general anaesthetics with very different molecular structures act in more or less identical ways, binding to the hydrophobic domains of proteins and altering their structures [34,35] . Matveev's account of the UCR has been related to microrheological changes in the cytoplasm and nucleoplasm and to advances in understanding of the role of heat shock proteins in cellular effects of stress [31] . There is indirect experimental support for a general cell-biological model of this kind [36,37] .…”

“…There is indirect experimental support for a general cell-biological model of this kind [36,37] . Another account, which on the face of it differs from that in [31,33] , has been proposed by Eïdus [31,[37][38][39] . Eïdus initially studied X-irradiation of mouse and Chinese hamster cells, including thymocytes, in vivo and in culture, measuring changes in (e.g.,) dry mass and loss of ability to form granules from neutral red dye [38,39] .…”

“…In all recent discussions of the UCR, this aspect is considered to be structure: the organization of the cytoskeleton and/or cytomatrix [31,33] or the barrier functions of plasma and intracellular membranes [32] . Perturbations of both these kinds are likely to coincide, and the remainder of the internal state will also be affected almost simultaneously.…”

“…This results in the negative effects of high stressor doses.) The adaptive or defensive character of the UCR could depend primarily on (plasma) membrane barrier function [32] or on cytomechanics and heat-shock proteins [31] , or, of course, on both mechanisms, which are presumably concurrent and complementary (cf. Fig.…”