Defining biological stress and stress responses based on principles of physics

Abstract

Stress represents a multi-faceted force that is central for the evolution of life. Organisms evolve while adapting to stress and stressful contexts often represent selective bottlenecks. To understand stress effects on biological systems and corresponding coping strategies it is imperative to properly define stress and the resulting strain that triggers compensatory responses in cells and organisms. Here I am deriving such definitions for biological systems based on principles that are established in physics. The relationship between homeostasis of critical biological variables, the elastic limit, the cellular stress response (CSR), cellular homeostasis response (CHR), system dysregulation, and the breaking point (death of the system) is outlined. Dysregulation of homeostatic set-points of biological variables perturbs the functional properties of the system, shifting them out of the evolutionarily optimized range. Such shifts are accompanied by elevated rates of macromolecular damage, which represents a non-specific signal for induction of a universal response, the CSR. The CSR complements the CHR in re-establishing homeostasis of the system as a whole. Moreover, the CSR is essential for coping with suboptimal conditions while the system is in a dysregulated state and for removing excessive damage that accumulates during such periods. The extreme complexity of biological systems and their emergent properties often necessitate monitoring stress effects on many biological variables simultaneously to properly deduce stress effects on the system as a whole. Therefore, increased utilization of systems biology (omics) This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Evolution of cellular stress response mechanisms

“…Following the definition of stress provided in the preceding article (Kültz, 2020) it is evident that the CSR only applies to stress severity that exceeds the elastic limit of cellular homeostasis. A CSR is only activated by severe stress that generates strain, which causes a proportional increase in macromolecular damage that disturbs cellular homeostasis.…”

COVID-19: A Redox Disease—What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment

“…A cardinal feature of the acute-phase response is the ability to maintain appropriate redox responses within the framework of the central coordinating response (215,216,375). Most aspects of metabolism and metabolic control are affected, but most important is the ability to protect those pathways central to maintaining homeostasis in the face of shifting metabolic demands (375,470).…”

“…The critical nutritional and metabolic capabilities supported by integration of the glutathione, peroxiredoxin and thioredoxin systems represent the fundamental determinant capability to provide protection and support/maintain Life (28,30,376). The pattern of nutrients required for the cellular stress response mechanisms have been clearly characterised at cellular and subcellular levels (215,216). It has been proposed that there is evidence for a central hub that plays a major role in controlling and determining cell fate (375).…”

Proteomics of osmoregulatory responses in threespine stickleback gills

“…The rationale underlying this distinction is that osmotic 350 homeostasis can by dysregulated in two directions, i.e. the homeostatic range or setpoint can be 351 surpassed during hyperosmotic stress or undercut during hypo-osmotic stress (Kültz 2020). 352 Therefore, specific responses to salinity changes are directional, i.e.…”

“…To isolate the influence of a particular environmental variable on the 96 gill proteome it is necessary to perform mesocosm experiments under controlled conditions using 97 appropriate controls (Somero 2012). Moreover, it is necessary to distinguish non-specific 98 responses to environmental change/ stress that may occur during acclimation to particular 99 environmental parameters from parameter-specific/ directional responses (Kültz 2020). The 100 present study isolates salinity-specific effects on the G. aculeatus gill proteome from those of 101 other environmental parameters and genetic differences that distinguish eco-and morpho-types.…”