Defining biological stress and stress responses based on principles of physics.

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 nonspecific 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) approaches for characterizing cellular and organismal stress responses facilitates the reductionist dissection of biological stress response mechanisms.