Yuliia V. Kolomiiets

Plant stress physiology has produced detailed descriptions of individual pathways—abscisic acid signalling, Ca²⁺ and reactive oxygen species networks, SnRK1 and TOR energy sensing, hormone crosstalk and transcriptional reprogramming—yet it still struggles to explain why the same stress elicits different outcomes in similar cells, why activation of protective pathways does not guarantee survival, and why recovery after stress is often incomplete. Here we argue that a missing integrative variable is the physicochemical state of the cytoplasm itself. We review evidence that cytosolic pH, ionic strength, energy charge, redox poise, macromolecular crowding, hydration and viscosity are regulated, stress-responsive quantities that control the assembly and material state of biomolecular condensates. Plant proteins including FLOE1, ELF3, phytochrome B, SEUSS, DCP5, subgroup I SnRK2 kinases, FUST1, RBGD2/4 and MBS1 sense hydration, temperature, crowding or singlet oxygen directly through phase behaviour, and condensates are now known to activate SnRK1, store and release autophagy proteins and control translation. Building on our previous theory of cytoplasmic phase homeostasis, we propose an integrative framework in which (i) cytoplasmic phase sensing acts as a distributed layer of stress perception; (ii) the phase state is coupled to the FLZ–SnRK1–TOR–autophagy network and may set the threshold and hysteresis of metabolic switching; (iii) the same state gates the mechanochemical capacity for cell expansion beyond the acid growth model; and (iv) the cytoplasmic phase reserve and the recovery trajectory determine resilience. We define six functional states, from the TOR-dominant growth state to adaptive reprogramming, immune–metabolic exhaustion, collapse and recovery, and grade every claim by level of evidence. Eight falsifiable hypotheses, with molecular markers, experimental designs and refutation criteria, are formulated, together with an integrated multiparameter measurement strategy and a prospective Plant Phase Homeostasis Index for resilience phenotyping.

Dental caries is a multifactorial disease mediated by a microbial biofilm, and it arises from the interaction of microbial metabolism, host defense mechanisms, salivary homeostasis and the mineral stability of enamel. Here we propose a multilevel molecular concept in which resistance to caries is defined by the capacity of the enamel–saliva–immunity–microbiome system to maintain mineral balance and to restore homeostasis after repeated acid loads. We identify seven interconnected functional nodes that determine the cariogenic activity of the biofilm: adhesion, synthesis of the extracellular matrix, acid production, acid tolerance, regulatory signaling, formation of alkaline metabolites, and interspecies metabolic cooperation. The key molecular mechanisms include the SpaP/PAc adhesins, the glucosyltransferases GtfB/GtfC/GtfD, phosphotransferase systems, lactate dehydrogenase, the F₁F₀-ATPase and the regulatory networks VicRK, LiaFSR, ComCDE/ComRS and CcpA. These processes are counteracted by salivary buffering systems, secretory IgA, antimicrobial proteins and microbial alkali-generating mechanisms, above all the arginine deiminase system and urease. We integrate molecular strategies directed at these vulnerabilities, including apigenin, tt-farnesol, epigallocatechin gallate, proanthocyanidins, structure-guided glucosyltransferase inhibitors, selective antimicrobial peptides (C16G2), arginine, fluoride and antigen-specific immunological approaches. We hypothesize that cariogenicity arises from a compensatory molecular network whose vulnerability depends on environmental conditions, metabolic redundancy and the spatial organization of the biofilm. Coordinated modulation of complementary targets may therefore suppress cariogenic functions more effectively than isolated blockade of single targets, while preserving the beneficial activity of the microbial community. The concept links molecular vulnerabilities with microbiome ecological resilience and enamel protection and yields experimentally testable predictions for multi-target caries prevention.

The acid growth hypothesis explains the role of apoplastic acidification in auxin-induced plant cell expansion; however, it does not, on its own, explain the conditions under which this process develops into sustained, irreversible growth. Apoplastic acidification, cell-wall loosening, and the presence of turgor pressure do not invariably result in the same growth response. This indicates that cell expansion should be understood as an outcome of interactions among hormonal regulation, cell-wall mechanical properties, water availability, and metabolic status. Here, we propose an integrative mechanistic model of plant cell expansion regulation in which the transition to a growth-permissive functional state is a central component. Within this framework, apoplastic pH is not considered a sufficient determinant of growth in itself, but rather a regulatory factor that influences the capacity of the cell wall to undergo mechanical deformation. The realization of growth depends on the coordination of this process with turgor pressure, water transport, metabolic capacity, and mechanosensory feedback mechanisms. This approach integrates the regulation of plasma membrane H⁺-ATPases, cell-wall remodelling, the TOR–SnRK1 signalling axis, and Ca²⁺- and reactive oxygen species-mediated pathways into a unified conceptual framework. The model describes cell expansion as a sequence of transitions among restricted, growth-permissive, actively expanding, and reinforcing states. Rather than rejecting the acid growth hypothesis, it extends its explanatory scope by linking local changes in apoplastic pH and cell-wall mechanics to the regulation of water relations, metabolism, and sustained growth. The proposed framework provides a basis for experimental investigation of the mechanisms through which plant cells convert regulatory signals into irreversible expansion.

Plant stress biology has traditionally relied on the analysis of snapshot measurements—including hormone levels, reactive oxygen species, transcripts, and physiological traits—which primarily characterize the current state of the cell, whereas the physical consequences of previous stress exposure remain considerably less accessible to direct measurement. This distinction may be particularly important under natural conditions, where plants experience recurrent, sequential, and combined stresses. This raises a fundamental question: can a cell, after physiological recovery, retain a measurable residual physical state that reflects aspects of its previous stress history and influences its response to subsequent stress? Here, we propose Environmental Phase Imprinting (EPI) as a testable biophysical hypothesis according to which environmental stress may leave a measurable imprint on the physical state of biomolecular condensates that persists after cessation of the initial exposure. EPI is not proposed as a new form of biological information or as an established mechanism of stress memory, but rather as a potential physical substrate, correlate, or consequence of previously described forms of cellular stress memory. To operationalize this hypothesis, we introduce the Plant Condensate Code (PCC), a multidimensional conceptual framework designed to move from a static “snapshot” of cellular state toward a time-resolved physical trajectory. PCC integrates complementary characteristics of condensate populations, including morphology, dynamics, molecular mobility, material state, and molecular composition, across a sequence of states encompassing baseline, stress, adaptation, recovery, and the post-stress state.We propose that the trajectory of condensate states, rather than any single measurement, may contain information about cellular stress history and may help explain differences in responses to recurrent or combined stress. Multimodal approaches, including live-cell imaging, fluorescence recovery after photobleaching (FRAP), molecular mobility analysis, microrheology, Brillouin microscopy, quantitative phase imaging, and molecular profiling, could provide complementary measurements of this physical state. PCC is further positioned within our broader conceptual research program encompassing Cytoplasmic Phase Homeostasis, Cytoplasmic Phase Sensing, and the Plant Threat Matrix (PTM)—a proposed six-state framework for describing plant physiological states under stress. Within this framework, physical measurements of condensate and cytoplasmic states may represent one possible approach for defining and quantitatively characterizing cellular physiological states. Finally, we discuss the potential application of this conceptual framework to stress-resilience phenotyping, evaluation of biostimulants, and selection for stress tolerance, while clearly distinguishing experimentally established phenomena from hypotheses and conceptual proposals. The proposed framework may provide a foundation for the development of a new direction in biophysical phenotyping of plant stress resilience, complementing molecular and physiological approaches to the study of stress memory.

Sunflower (Helianthus annuus L.) is one of the major oilseed crops cultivated in Ukraine, particularly in the southern and steppe regions, where agricultural soils have been affected by military activities and explosive disturbance. These environments expose plants to complex combinations of chemical and physical stressors, including heavy metals, nitroaromatic explosives, perchlorates, soil structural disruption, and thermal and oxidative perturbations. Classical models of plant stress responses largely conceptualize stressors as independent inputs acting through parallel signaling pathways and scaling approximately with stress intensity. Such a framework is insufficient for describing plant responses to combined stress, because multiple stressors converge on shared regulatory, metabolic, energetic, and biophysical networks. In this work, we propose a conceptual model of stress emergence in plants under the action of multiple interacting stressors, termed the Plant Threat Matrix (PTM). Within this framework, the plant is conceptualized as a multistable nonlinear adaptive system that transitions between discrete physiological attractor states—from active growth (S1), through a pre-stress priming window (PSW), moderate adaptive stress (S2), immune–metabolic exhaustion (S3), and ultimately irreversible collapse (CS). The unifying architecture is represented by the SA–JA/ET–ABA–TOR immune–metabolic network, with LLPS-mediated sensing, ABA–TOR antagonism involving the SnRK2→SnRK1→RAPTOR cascade, SOURCE–SINK disruption associated with reduced CWIN activity, and FLZ proteins as candidate modulators of SnRK1 activity. Within this framework, post-explosive contaminants are considered interacting destabilizing factors rather than independent toxicants, capable of driving plants toward chronic immune–metabolic exhaustion through combined oxidative stress, altered phase behavior, protein aggregation, and energetic depletion. The PTM provides a general framework for explaining how interacting stressors can drive transitions between adaptive, exhausted, and collapse states. The framework further provides a basis for phase-oriented agronomic management and for developing quantitative threshold datasets for sunflower and other oilseed crops exposed to combined environmental stress.

Current paradigms of plant stress response fail to explain how diverse physical perturbations—such as hydration shifts, macromolecular crowding, temperature variations, and ionic dynamics—integrate into unified metabolic outcomes. Here, we present a novel conceptual framework asserting that the physical state of the cytoplasm acts as a master intermediate variable coupling environmental cues to cellular signaling and recovery. We propose that distinct physical sensing events (exemplified by FLOE1, DCP5, and ELF3) conceptually converge onto the central SnRK1–TOR metabolic switch. Within this architecture, we identify the FCS-LIKE ZINC FINGER (FLZ) protein family as a key molecular state buffer that modulates the activation threshold, amplitude, and reversibility of SnRK1–TOR signaling. Leveraging established FLZ–SnRK1 interactions and ATG8-dependent FLZ degradation, we formalize a self-reinforcing positive-feedback loop driven by autophagy that stabilizes metabolic transitions. Crucially, while avoiding premature claims of FLZ proteins as direct phase sensors, we define the FLZ–SnRK1–TOR–autophagy axis as a critical biophysical-to-metabolic interface. This work unifies traditionally fragmented biological tiers into a single mechanistic cascade spanning environmental stress factors, cytoplasmic biophysics, biomolecular condensate dynamics, molecular signaling, SnRK1–TOR metabolic switching, autophagy, and ultimate cellular adaptation. Ultimately, this state-centric paradigm shifts crop biotechnology from conventional gene-expression maximization toward precise biophysical threshold engineering and stress-recovery optimization.

How does a cell preserve information about its own organization that is required to reconstruct a functional state after reversible cessation of activity? This question extends beyond the traditional view of cellular survival as the preservation of molecular components. Cellular recoverability depends not only on the preservation of proteins, membranes, DNA, and organelles, but also on the preservation of organizational information that determines how these components must be spatially, structurally, and functionally reassembled after the cell exits a stabilized or metabolically suppressed state. Here, we develop Structural Recovery Information Theory (SRIT), a new conceptual theory proposing that cells preserve not only molecular information but also information about the relationships among molecular components that maintain the possibility of subsequent functional reconstruction. The central concept of SRIT is Structural Recovery Information (SRI), defined as a distributed informational property of cellular organization that determines or constrains possible trajectories of recovery following reversible physiological or metabolic arrest. Unlike genetic, epigenetic, transcriptional, and stress memory, SRI is neither a molecule nor a discrete structure or localized information carrier; rather, it may be instantiated through organelle positioning, membrane architecture, macromolecular complexes, protein–protein interactions, phase-separated condensates, cytoskeletal organization, proteostasis, local metabolite concentrations, molecular crowding, and the physical state of the cytoplasm. Thus, whereas modern biology has traditionally conceptualized biological information primarily through the DNA → RNA → protein paradigm, SRIT extends this view by emphasizing that cellular function depends on the integrated organization of molecules, spatial relationships, interactions, phase state, topology, and dynamics. The theory distinguishes cellular viability, structural integrity, recovery competence, and functional recovery, and conceptualizes recovery as a process involving not only metabolic reactivation but also reconstruction of functional organization. To characterize alternative outcomes following reversible arrest, we introduce the Cellular Recovery Landscape, while Recovery Information Integrity (RII) is proposed as a conceptual framework for the future quantitative operationalization of recovery-relevant organizational information. An important extension of SRIT is cytoskeletal–mechanical organization, which represents one of the most experimentally tractable potential substrates of SRI; actin and microtubule networks, motor proteins, crosslinkers, organelle positioning, and membrane–cytoskeleton interactions may provide spatial and mechanical constraints required for restoration of cellular architecture. On this basis, we propose the Cytoskeletal Recovery Scaffold (CRS) as a specific, testable example of a potential physical substrate of SRI. Within this framework, cellular recovery is viewed as constrained by the amount, integrity, and reconstructability of organizational information preserved during reversible cellular arrest. This perspective extends the problem of cellular recovery beyond desiccation and provides a unified conceptual framework for examining anhydrobiosis, hypometabolism, spores, seeds, cryopreservation, hibernation, anoxia, extreme cold, transient cellular arrest, stress-induced metabolic suppression, and cellular dormancy. SRIT therefore proposes that a cell should be understood not merely as a collection of preserved molecules, but as an organized system that must preserve sufficient information about its own architecture to regain a functional state.

Plant cells are commonly described as sensing environmental stress through specialized molecular receptors that initiate canonical signalling cascades ultimately leading to transcriptional reprogramming. Although this receptor-centred view is strongly supported by experimental evidence, it leaves an explanatory gap: many physiological adjustments to dehydration, heat and cold stress, as well as osmotic imbalance, begin within seconds to minutes—substantially earlier than receptor-initiated transcription could plausibly account for these changes. Over the past decade, studies of biomolecular condensates and liquid–liquid phase separation (LLPS) have shown that numerous plant and non-plant proteins can change their material state—from freely diffusing monomers to liquid droplets, gels, or glass-like states—directly in response to the same physicochemical variables that stress imposes on the cytoplasm: hydration, ionic strength, pH, redox potential, macromolecular crowding, and temperature. These phenomena are typically considered separately for individual types of condensates, without an explicit conceptual layer linking the physical state of the cytoplasm as a whole to the classical Ca²⁺–ROS–hormone–transcription signalling architecture. In this work, we synthesize existing experimental and theoretical evidence and propose the concept of Cytoplasmic Phase Sensing (CPS), on the basis of which we develop the Cytoplasmic Phase Sensing Theory (CPST). The theory proposes that a living plant cell can convert environmentally induced physicochemical perturbations into regulated changes in cytoplasmic phase organization, molecular mobility, and material state, and that these transitions contribute to shaping subsequent metabolic, hormonal, and transcriptional responses. As the strongest currently available mechanistic example, we consider dehydration, examining established patterns of macromolecular crowding, liquid–liquid phase separation (LLPS), stress granules, mechanosensitive channels, Ca²⁺/ROS/ABA/TOR–SnRK1 signalling pathways, and stress memory. We explicitly distinguish experimentally established evidence, mechanistic inferences, and the new hypothesis proposed in this work. We identify what is genuinely novel in this concept relative to existing approaches—including classical homeostasis, proteostasis, receptor-mediated signalling, mechanosensing, and LLPS biology when considered separately—and formulate falsifiable and methodologically testable predictions, complemented by a discussion of the strongest arguments against the proposed concept. Cytoplasmic Phase Sensing is presented not as an established mechanism, but as a structured hypothesis intended to organize future experimental research at the interface of plant stress physiology and cellular biophysics.

Biological stress and aging are traditionally understood primarily through stressor-specific molecular mechanisms, including osmoregulation, stress-signaling pathways, proteostasis impairment, mitochondrial dysfunction, membrane remodeling, and cellular senescence. Despite substantial differences in their initiating mechanisms, diverse stressors and age-related changes are often accompanied by a common functional consequence: a reduced capacity of the cell to reversibly reorganize its intracellular environment and restore a functionally competent state after stressor removal. Here, we propose a unified biophysical theory of aging and stress based on phase plasticity, which considers the capacity of cellular matter to undergo controlled and reversible physical reorganization as a potential integrative level linking molecular mechanisms with functional recovery. The central concept of the model is phase plasticity, defined as the capacity of the cytoplasm, membranes, biomolecular condensates, and intracellular compartments to transition between functionally distinct physical states while retaining the capacity for reversible restoration. On this basis, Phase Rigidity Syndrome (PRS) is introduced as a hypothetical integrative state that may emerge from the progressive and cumulative loss of phase plasticity. We propose that phase rigidity is associated with reduced molecular mobility, altered biomolecular condensate dynamics, impaired membrane fluidity, diminished proteostatic capacity, and delayed or incomplete recovery following stress. Under prolonged or repeated stress, these changes may mutually reinforce one another, promoting a transition from adaptive phase reorganization toward persistent phase rigidity and, under extreme conditions, phase collapse. The theoretical framework integrates the concepts of phase homeostasis, phase buffer, phase resilience, phase recovery, phase memory, phase threshold, and phase-transition window, and introduces a conceptual Phase Resilience Index (PRI) for characterizing the capacity of cells to maintain and restore phase organization. Importantly, PRS is not proposed as an established biological or clinical syndrome, nor is phase plasticity presented as a validated universal variable. Rather, the proposed framework represents a research hypothesis that requires experimental testing. The proposed theory does not replace existing molecular models of cellular stress and aging but introduces an additional biophysical level of integration, at which distinct primary perturbations may partially converge through changes in the capacity of cellular matter to undergo reversible physical reorganization. The scientific value of the framework will ultimately depend on whether measures of phase plasticity provide additional predictive information on cellular resilience and recovery beyond established molecular markers of stress and aging.