Review Reports - Adaptation Begins at the Wall: Hormonal Control of Cell-Wall Plasticity Under Abiotic Stresses

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Article entitled ‘Hormone-Mediated Cell Wall Metabolism Under Abiotic Stress: Molecular Mechanisms, Signaling Networks, and Opportunities for Climate-Resilient Crops

The study analyse the effects of hormones in modulating cell wall metabolism, molecular Mechanisms, signaling networks, under the event of abiotic Stress. The review is emphasizing that abiotic stress adaptation to be viewed as a dynamic feed-back network connecting environmental perception, cell-wall integrity sensing, hormone signaling, and wall remodeling

This review contains lot of information, however, lack methodological novelty as mentioned below in major/minor comments-

Abstract:

Introduction and other sections

Line 56-57: need restructuring ‘biotic stress creates a fundamental allocation problem: plants must protect cellular integrity and conserve resources without permanently sacrificing growth and reproduction.’; The punctuations may be removed and continuous sentence will be better

Line 59: Correct Ca2+ (Superscript) and elsewhere (line 211 etc) peroxide under scripts may be rectified

Section 1.3. The purpose of review is not clear and how it differs from other meta-analysis. Methodology section must be provided that what type review it is and exclusion/inclusion criteria.

Line- 241- “ABA-responsive MYB factors” it is better to add connecting word between sentences rather than abruptly using abbreviated hormone name

Section 4.1. Use expanded form of ABA in sub-heads

-Line 413-414: Check spacing

-The abiotic stresses are discussed for metals etc with plethora of information, however, the critical, comparative, and analytical prospects are lacking.

Author Response

Response to Reviewer 1 Comments

Dear Reviewer,

We sincerely thank the reviewer for their thorough and constructive evaluation of our manuscript. Their insightful comments and suggestions have substantially strengthened the scientific depth, clarity, and overall presentation of our work, and we are grateful for the time and expertise they have invested in this review. We have carefully considered each comment and revised the manuscript, accordingly, as detailed in our point-by-point responses below. For ease of evaluation, all changes made in response to Reviewer 1's comments are highlighted in Yellow, in the revised manuscript. We believe these revisions have significantly improved the manuscript, and we hope it now meets the standards for publication in Biomolecules.

General comment. Article entitled ‘Hormone-Mediated Cell Wall Metabolism Under Abiotic Stress: Molecular Mechanisms, Signaling Networks, and Opportunities for Climate-Resilient Crops. The study analyse the effects of hormones in modulating cell wall metabolism, molecular Mechanisms, signaling networks, under the event of abiotic Stress. The review is emphasizing that abiotic stress adaptation to be viewed as a dynamic feed-back network connecting environmental perception, cell-wall integrity sensing, hormone signaling, and wall remodeling. This review contains lot of information, however, lack methodological novelty as mentioned below in major/minor comments-

Response: Thank you for the reviewer’s overall assessment and for recognizing the breadth and relevance of the review. We agree that, although the manuscript provides a comprehensive synthesis of hormone-mediated cell-wall remodeling and CWI signaling under abiotic stress, its methodological and conceptual novelty needed to be stated more clearly. In the revised manuscript, we have therefore strengthened the review framework by explicitly organizing the evidence around a causal sequence linking stress perception, hormone signaling, cell-wall remodeling, CWI sensing, physiological responses, and whole-plant performance. We have also clarified the evidence grading, distinguished experimental systems and levels of inference, refined the literature-selection strategy, and revised the figures to better separate the whole-plant conceptual framework from the molecular CWI signaling module. These changes are intended to make the review’s integrative methodological approach and conceptual contribution more explicit.

Abstract:

Response: Thank you for the positive assessment of the Abstract.

Major comments:

Comment 1. Introduction and other sections, Line 56-57: need restructuring ‘biotic stress creates a fundamental allocation problem: plants must protect cellular integrity and conserve resources without permanently sacrificing growth and reproduction.’; The punctuations may be removed and continuous sentence will be better.

Response: Thank you for the suggestion. The sentence has been restructured to improve readability and flow by removing the colon and making it a continuous sentence. The revised sentence now reads: Abiotic stress creates a fundamental allocation problem in which plants must protect cellular integrity and conserve resources without permanently sacrificing growth and reproduction.

Comment 2. Line 59: Correct Ca2+ (Superscript) and elsewhere (line 211 etc) peroxide under scripts may be rectified.

Response: Thank you for pointing this out. The notation for Ca²⁺ has been corrected using superscript formatting, and H₂O₂ and other chemical formulas have been standardized throughout the manuscript using appropriate superscript and subscript formatting.

Comment 3. Section 1.3. The purpose of review is not clear and how it differs from other meta-analysis. Methodology section must be provided that what type review it is and exclusion/inclusion criteria.

Response: Thank you for this important comment. We have revised Section 1.3 to clearly state the purpose, scope, and distinct contribution of the review. The revised section now explains that the review integrates fragmented evidence on phytohormone signaling, cell-wall integrity sensing, and cell-wall remodeling into a unified mechanistic framework for abiotic-stress adaptation. We have also clarified that this work is a mechanistic integrative narrative review rather than a quantitative meta-analysis, as it does not statistically pool effect sizes from comparable datasets. In addition, in 1.3 a new section Literature Search and Selection Strategy,” has been added to describe the literature sources, search concepts, inclusion and exclusion criteria, and the rationale for qualitative mechanistic synthesis.

Comment 4. Line- 241- “ABA-responsive MYB factors” it is better to add connecting word between sentences rather than abruptly using abbreviated hormone name

Response: Thank you for this helpful suggestion. We have revised the sentence by adding an appropriate connecting word and by introducing the hormone name more smoothly. The revised text now reads: “Moreover, abscisic acid (ABA)-responsive MYB transcription factors regulate environmentally induced endodermal suberization in Arabidopsis, thereby providing a direct link between hormonal signaling and barrier formation

Comment 5. Section 4.1. Use expanded form of ABA in sub-heads

Response: Thank you for the suggestion. The abbreviation ABA in the subsection heading has been expanded to its full form. The revised heading now reads: 4.1. Abscisic Acid: Wall Reinforcement, Lignification, Suberization, and Water-Deficit Adaptation.

Comment 6. -Line 413-414: Check spacing

Response: Thank you for pointing this out. The spacing issue in Lines 413–414 has been carefully checked and corrected to ensure consistent formatting and readability.

Comment 7. -The abiotic stresses are discussed for metals etc with plethora of information, however, the critical, comparative, and analytical prospects are lacking.

Response: Thank you for this insightful comment. We agree that the previous version provided extensive descriptive information on individual abiotic stresses but lacked sufficient critical comparison and analytical synthesis across stress types. To address this concern, we have added a new subsection, 6.8. Critical Comparative Synthesis and Analytical Prospects, in which we compare the distinct cell-wall responses associated with drought, salinity, heat, cold/freezing, flooding, heavy-metal and nutrient-associated stresses, and combined stresses. The revised section now emphasizes that no single stress-tolerant wall phenotype applies across all stresses and highlights the importance of tissue specificity, timing, reversibility, and physiological trade-offs. We also compare the relative strength of mechanistic evidence among stress classes, distinguishing well-supported pathways such as FER-dependent Ca²⁺ signaling under salinity, ABA-linked wall regulation under drought, ethylene-mediated wall loosening during flooding, and EIN3–XTH33 regulation under cadmium stress from areas where evidence remains largely correlative. Finally, we have added analytical recommendations for future studies, including time-resolved, factorial, and sequential experimental designs integrating hormone signaling, wall mechanics, polymer composition, transport processes, and growth or yield outcomes. These revisions substantially strengthen the critical, comparative, and analytical perspective of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Manuscript title: “Hormone-Mediated Cell Wall Metabolism Under Abiotic Stress: Molecular Mechanisms, Signaling Networks, and Opportunities for Climate-Resilient Crops”

Recommendation: Major Revision

This manuscript presents a broad and timely review of the interactions between phytohormonal signaling, cel wall remodeling, cel wall integrity (CWI) sensing, and plant adaptation to abiotic stress. This is a valuable conceptual framework and is consistently reflected in the manuscript, however, in its current form, the manuscript requires major revision before it can be considered for publication.

- The central conceptual advance should be made more explicit

The strongest conceptual message of the review is that stress tolerance does not simply result from stronger or weaker cell walls, but from context dependent regulation of wall properties according to tissue identity, developmental stage, stress intensity, and stress duration. This idea is stated several times throughout the manuscript and is also reflected in Figures 1 and 4. However, the large amount of descriptive information concerning individual hormones, wall polymers, receptors, and enzymes sometimes obscures this central message.

The authors should consider restructuring parts of the review around the following causal framework: Abiotic stress → environmental/mechanical perturbation → CWI/hormone perception → signaling → specific wall remodeling → mechanical/physiological phenotype → whole plant performance

- The link between molecular remodeling and actual cell wall mechanics should be strengthened

This is an important conceptual issue. The manuscript frequently describes:

cellulose synthesis;
pectin methylesterification;
lignification;
suberization;
expansin activity;
XTH activity;

but the actual mechanical consequences are sometimes inferred rather than directly demonstrated. The authors themselves correctly state that transcriptional changes do not necessarily demonstrate changes in wall mechanics. Therefore, the review should more systematically distinguish molecular wall phenotype from biochemical wall phenotype and mechanical wall phenotype.

- Hormone crosstalk should be presented more mechanistically

Section 5 is conceptually important, and the authors correctly state that hormone pathways rarely operate independently. However, several subsections remain largely descriptive.

For example, the ABA - auxin section would benefit from a clearer distinction between:

hormone concentration;
hormone transport;
hormone sensitivity;
receptor signaling;
downstream transcription;
wall remodeling.

The same applies to ABA - ethylene and JA - ethylene/SA interactions.

The statement that “hormone ratios and receptor context are often more informative than absolute hormone abundance” is interesting, but it should be supported with specific examples and, where possible, quantitative evidence.

- Combined and sequential stresses require a more critical discussion

The discussion of combined and sequential stresses is timely and potentially one of the most valuable aspects of the review. However, the authors should distinguish more explicitly between:

simultaneous combined stresses;
sequential stresses;
fluctuating stresses;
stress recovery cycles;
stress memory.

These issues can activate different signaling networks and produce different wall phenotypes.

The authors should also discuss whether the currently available experimental evidence directly demonstrates altered wall remodeling under combined stresses or whether the proposed mechanisms are mainly extrapolated from single stress studies.

- Figures 1 and 2 partly overlap

Figures 1 and 2 are conceptually strong and visually informative. However, there is some overlap between them.

Figure 1 presents the general:

stress → hormones → wall remodeling → CWI → physiological outcome

framework.

Figure 2 presents:

wall perturbation → CWI receptors → Ca²⁺/ROS/MAPK/hormones → transcription → wall remodeling → restored homeostasis.

The authors should make the distinct purpose of each figure more explicit, or consider simplifying one of them.

Figure 1 could remain the whole plant conceptual framework, whereas Figure 2 could be explicitly presented as the molecular CWI signaling module.

- Specific comments by section

Section 2 - Cell Wall Architecture and Remodeling

This section is comprehensive and scientifically useful.

A particularly positive aspect is the distinction between Type I and Type II cell walls and the warning against directly transferring Arabidopsis/eudicot mechanisms to cereals. The discussion of pectin methyl esterification is also appropriately nuanced: PME activity should not simply be described as either “wall stiffening” or “wall loosening”. However, the section could be shortened.

Section 3 - Sensing Cell Wall Perturbation

This is one of the strongest sections of the manuscript. The distinction between mechanoperception and CWI sensing is useful. The treatment of FERONIA is also appropriately cautious. The authors correctly avoid presenting FER as a universal mechanoreceptor. I recommend retaining this section essentially in its current conceptual form while strengthening the distinction between direct ligand/receptor evidence and inferred mechanical sensing.

Section 5 - Hormone Crosstalk

early signaling → intermediate remodeling → prolonged structural adaptation → recovery.

This would also connect nicely with the manuscript's discussion of fluctuating and sequential stresses.

Section 7 - Molecular Control

The discussion of transcriptional, post transcriptional and epigenetic regulation is appropriate.

However, the authors should be cautious about implying that changes in transcript abundance necessarily result in altered wall properties.

Where possible, the review should follow the chain:

gene expression → protein/enzyme activity → polymer chemistry → wall mechanics → phenotype.

Minor comments

Minor Comment 1

- The manuscript should undergo thorough English editing. Several grammatical and typographical errors remain.

On page 16/line 511, the sentence: “Representative hormone wall mechanisms, biological contexts, and evidence anchors are brief explain in Table 2.” should be corrected to:

“Representative hormone wall mechanisms, biological contexts, and evidence anchors are briefly summarized in Table 2.”

- The manuscript should consistently distinguish evidence obtained from intact plants from experiments using cell cultures, seedlings, inhibitors, or mutant lines.

- The authors should carefully check all references for consistency of journal names, author names, DOI information, year, volume, and article numbers.

- The terminology for gibberellin should be standardized between “GA” and “GAs” according to whether a specific molecule or the hormone class is intended.

Author Response

Response to Reviewer 2 Comments

Dear Reviewer,

We sincerely thank the reviewer for their thorough and constructive evaluation of our manuscript. Their insightful comments and suggestions have substantially strengthened the scientific depth, clarity, and overall presentation of our work, and we are grateful for the time and expertise they have invested in this review. We have carefully considered each comment and revised the manuscript, accordingly, as detailed in our point-by-point responses below. For ease of evaluation, all changes made in response to Reviewer 2's comments are highlighted in Red, in the revised manuscript. We believe these revisions have significantly improved the manuscript, and we hope it now meets the standards for publication in Biomolecules.

Major comments:

Comment 1.Manuscript title: “Hormone-Mediated Cell Wall Metabolism Under Abiotic Stress: Molecular Mechanisms, Signaling Networks, and Opportunities for Climate-Resilient Crops”

Recommendation: Major Revision

Response: Thank you for this comprehensive and constructive assessment. We appreciate the reviewer’s recognition of the manuscript’s timely scope and conceptual framework. In response to the concerns raised, we have substantially revised the manuscript to improve clarity, consistency, mechanistic precision, evidence interpretation, terminology, figure organization, and the distinction between different experimental systems and levels of evidence. We believe these revisions have significantly strengthened the manuscript and addressed the major issues identified by the reviewer.

Comment 2. - The central conceptual advance should be made more explicit

Response: Thank you for your valuable suggestion. To address this point, we have strengthened the conceptual framework of the manuscript so that the review is now explicitly organized around the causal sequence: abiotic stress, environmental/mechanical perturbation, stress and cell-wall integrity (CWI) sensing, hormone and second-messenger signaling , specific cell-wall remodeling, mechanical or transport phenotype, physiological response, whole-plant performance. We have emphasized throughout the revised manuscript that stress tolerance does not arise from uniformly stronger or weaker walls, but from context-dependent regulation of wall properties according to tissue identity, developmental stage, stress intensity, and stress duration. This principle is now stated more clearly in the introductory conceptual framework, reinforced in the stress-comparison section, and carried through to the future research priorities and conclusion.

Comment 3. - The link between molecular remodeling and actual cell wall mechanics should be strengthened

This is an important conceptual issue. The manuscript frequently describes:

cellulose synthesis;
pectin methylesterification;
lignification;
suberization;
expansin activity;
XTH activity;

Response: Thank you for this thoughtful and constructive assessment. We agree that the central conceptual contribution of the review needed to be made more explicit and that the distinction between molecular remodeling and directly demonstrated wall mechanics required clearer treatment. To address this point, we have added a new subsection entitled 2.5. Linking Molecular Remodeling to Biochemical, Mechanical, and Physiological Phenotypes. This section explicitly distinguishes molecular/regulatory phenotypes, biochemical or structural wall phenotypes, mechanical or transport phenotypes, and physiological/whole-plant outcomes. We now clarify that changes in expression or activity of genes and proteins involved in cellulose synthesis, pectin methylesterification, lignification, suberization, expansin activity, or XTH activity should not automatically be interpreted as evidence of altered wall mechanics. Where direct biomechanical or transport measurements are lacking, the corresponding mechanical consequence is described as inferred rather than demonstrated. We also revised the hormone-centered sections to apply this same evidence hierarchy consistently.

Comment 4. - Hormone crosstalk should be presented more mechanistically

Section 5 is conceptually important, and the authors correctly state that hormone pathways rarely operate independently. However, several subsections remain largely descriptive.

For example, the ABA - auxin section would benefit from a clearer distinction between:

hormone concentration;
hormone transport;
hormone sensitivity;
receptor signaling;
downstream transcription;
wall remodeling.

The same applies to ABA - ethylene and JA - ethylene/SA interactions.

Response: Thank you for this helpful comment. You are right that the earlier version of Section 5 leaned too heavily on description and did not clearly separate the different levels at which hormones interact. We have rewritten the section around that distinction. It now treats hormone concentration and biosynthesis, transport and spatial distribution, tissue sensitivity, receptor and signaling activity, downstream transcription, cell-wall remodeling, and the resulting mechanical or physiological output as separate layers.

We applied this framework to the ABA–auxin, ABA-ethylene, and JA-ethylene/SA subsections. In each one, we now keep changes in hormone abundance apart from changes in signaling and wall behavior, and we give specific examples of how receptor activity, transcriptional regulation, wall-remodeling processes, and physiological responses link together. Where the data allowed, we also added time-resolved and quantitative examples, including ethylene-dependent expansin regulation during submergence and the strong JA response to cell-wall perturbation. Finally, we reworded the statement on hormone ratios and receptor context, which went further than the evidence supports. The revised text now says that relative hormonal state and signaling context are often more informative than hormone abundance alone. Together, these changes make Section 5 more mechanistic and show more clearly how hormone signaling, cell-wall remodeling, and stress adaptation are connected.

Comment 5. - Combined and sequential stresses require a more critical discussion

The discussion of combined and sequential stresses is timely and potentially one of the most valuable aspects of the review. However, the authors should distinguish more explicitly between:

simultaneous combined stresses;
sequential stresses;
fluctuating stresses;
stress recovery cycles;
stress memory.

These issues can activate different signaling networks and produce different wall phenotypes.

Response: Thank you for this helpful comment. We agree that the previous version did not clearly separate the different ways plants experience multiple stresses over time. We have therefore revised Section 6.7 to distinguish simultaneous combined stress, sequential stress, fluctuating stress, stress–recovery cycles, and stress memory, and to explain why each can involve different signaling pathways and cell-wall responses. We also strengthened the discussion of the available evidence. The revised section now separates studies that directly show changes in wall composition or structure from those in which wall responses are mainly inferred from single-stress studies. We added examples involving combined heat and osmotic stress, combined heat and drought, wall changes during rewatering, and persistent wall-associated changes after salt adaptation. At the same time, we make clear that direct biomechanical evidence and complete causal links from hormone/CWI signaling to wall remodeling and whole-plant performance are still limited.

We further clarify that stress memory is different from simple sequential exposure or incomplete recovery, because it requires a lasting effect of an earlier stress that changes the response to a later one. Finally, we added recommendations for factorial and time-resolved experiments that compare single, simultaneous, sequential, fluctuating, recovery, and re-stress conditions. These revisions make the section more critical and better distinguish directly demonstrated wall responses from those that remain inferred or hypothetical.

Comment 6. - Figures 1 and 2 partly overlap

Figures 1 and 2 are conceptually strong and visually informative. However, there is some overlap between them.

Figure 1 presents the general:

stress → hormones → wall remodeling → CWI → physiological outcome

framework.

Figure 2 presents:

wall perturbation → CWI receptors → Ca²⁺/ROS/MAPK/hormones → transcription → wall remodeling → restored homeostasis.

The authors should make the distinct purpose of each figure more explicit, or consider simplifying one of them.

Figure 1 could remain the whole plant conceptual framework, whereas Figure 2 could be explicitly presented as the molecular CWI signaling module.

Response: Thank you for this helpful comment. We agree that Figures 1 and 2 previously showed some conceptual overlap. Figure 1 has therefore been revised to emphasize the whole-plant, systems-level framework linking abiotic stress, hormone signaling, cell-wall remodeling, physiological responses, and plant performance. The detailed molecular CWI components have been simplified in Figure 1 and are now represented as wall-status sensing, signal integration, and feedback regulation. Figure 2 is retained as the dedicated molecular CWI signaling module, showing receptor-mediated sensing and downstream Ca²⁺, ROS, MAPK, hormone, and transcriptional responses. This revision makes the distinct purpose of each figure more explicit and reduces redundancy.

Comment 7. - Specific comments by section

Section 2 - Cell Wall Architecture and Remodeling

This section is comprehensive and scientifically useful. A particularly positive aspect is the distinction between Type I and Type II cell walls and the warning against directly transferring Arabidopsis/eudicot mechanisms to cereals. The discussion of pectin methyl esterification is also appropriately nuanced: PME activity should not simply be described as either “wall stiffening” or “wall loosening”. However, the section could be shortened.

Response: Thank you for this helpful suggestion. We agree that Section 2 was more detailed than it needed to be. We have now shortened Sections 2.1–2.4 by removing repeated background information and keeping the points most relevant to the main focus of the review. We retained the important distinction between eudicot Type I and grass Type II cell walls and the caution that findings from Arabidopsis should not be transferred directly to cereal crops. We also kept the balanced discussion of PME activity, since its effect can vary with Ca²⁺ availability, apoplastic pH, spatial patterning, enzyme context, and tissue type. Overall, the revised section is shorter and clearer while keeping the key scientific and crop-related messages.

Comment 8. Section 3 - Sensing Cell Wall Perturbation

Response: Thank you for this positive and helpful comment. We kept the overall structure of Section 3 but sharpened the line between direct receptor evidence and inferred mechanical sensing. The revised text now separates three kinds of evidence: direct ligand–receptor or receptor–wall interactions, functional evidence that a receptor is required for a CWI response, and cases where mechanical sensing is only inferred from changes in wall stiffness, turgor, deformation, or stress responses. We also make two points explicit. Direct ligand binding does not, by itself, show that a receptor senses mechanical force. Likewise, a receptor-dependent stress phenotype does not necessarily reveal which physical cue is being sensed. We applied these distinctions to FER, THE1, MIK2, the WAKs, and RALF-associated receptor complexes. Throughout, we kept our cautious reading of FER as one component of a broader CWI signaling network and not a universal mechanoreceptor

Comment 9. Section 5 - Hormone Crosstalk

I particularly support the statement that hormone crosstalk should be considered as a trajectory rather than a single sampling point. However, this principle could be developed further using a conceptual temporal model, for example: early signaling → intermediate remodeling → prolonged structural adaptation → recovery. This would also connect nicely with the manuscript's discussion of fluctuating and sequential stresses.

Response: Thank you for this helpful suggestion. We agree that the temporal nature of hormone crosstalk deserved a clearer conceptual treatment. We have therefore expanded Section 5.6 around a temporal framework of early signaling, intermediate remodeling, prolonged structural adaptation, recovery. The revised discussion links this temporal model with fluctuating and sequential stresses, where a new stress may occur before the previous hormonal or wall state has fully returned to baseline, potentially contributing to stress memory. This addition strengthens the connection between hormone crosstalk, temporal wall plasticity, and complex field-like stress histories.

Comment 10. Section 7 - Molecular Control

The discussion of transcriptional, post transcriptional and epigenetic regulation is appropriate.

However, the authors should be cautious about implying that changes in transcript abundance necessarily result in altered wall properties.

Where possible, the review should follow the chain: gene expression → protein/enzyme activity → polymer chemistry → wall mechanics → phenotype.

Response: Thank you for this important comment. We agree that changes in transcript abundance should not be interpreted automatically as changes in cell-wall properties. We have therefore revised Section 7 to make the evidence chain more explicit and to distinguish regulatory changes from downstream biochemical, mechanical, and physiological outcomes. Where the available evidence allows, the revised discussion now follows the sequence from gene expression to protein or enzyme activity, polymer chemistry or wall architecture, wall mechanics or transport properties, and finally phenotype.

Minor comments

Comment 1. - The manuscript should undergo thorough English editing. Several grammatical and typographical errors remain. On page 16/line 511, the sentence: Representative hormone wall mechanisms, biological contexts, and evidence anchors are brief explain in Table 2. should be corrected to: “Representative hormone wall mechanisms, biological contexts, and evidence anchors are briefly summarized in Table 2.

Response: Thank you for this careful observation. Then sentence has been corrected in the revised manuscript. We have also carefully proofread the manuscript and corrected additional grammatical and typographical errors throughout to improve clarity and language quality.

Comment 2. - The manuscript should consistently distinguish evidence obtained from intact plants from experiments using cell cultures, seedlings, inhibitors, or mutant lines.

Response: Thank you for this valuable comment. We have revised the manuscript to clearly distinguish evidence from intact or whole plants from findings obtained using seedlings, cell cultures, inhibitors, and mutant lines. The experimental system is now specified where relevant, and conclusions from cellular or model-based studies are presented more cautiously rather than being interpreted as direct evidence of whole-plant responses.

Comment 3. - The authors should carefully check all references for consistency of journal names, author names, DOI information, year, volume, and article numbers.

Response: Thank you for this important comment. We have carefully checked and standardized all references throughout the manuscript. Journal names, author names, publication years, volume and issue information, page ranges or article numbers, and DOI details were verified and corrected where necessary to ensure consistency and accuracy according to the journal’s reference style.

Comment 4.- The terminology for gibberellin should be standardized between “GA” and “GAs” according to whether a specific molecule or the hormone class is intended.

Response: Thank you for this comment. We have carefully checked the manuscript and standardized the terminology related to gibberellins. GAs is now used when referring to gibberellins as a hormone class, whereas GA is used only when referring to a specific gibberellin molecule.

Reviewer 3 Report

Comments and Suggestions for Authors

This review addresses a fundamental and highly relevant issue in modern plant physiology: the integration of hormonal signals and the mechanical state of the cell wall (CWI) in the context of global climate change. The authors successfully move beyond the traditional paradigm—which views the cell wall merely as a passive scaffold—to present it instead as a dynamic sensory-signaling matrix. The manuscript follows a logical progression: starting with the basic composition of polymers and remodeling enzymes, moving to cell wall integrity (CWI) control systems and complex phytohormone interaction networks, and concluding with applied aspects of crop breeding.

Unlike existing reviews that focus either exclusively on polysaccharide biochemistry or on specific hormonal pathways, this work employs a profound systems-level approach that integrates biomechanics, molecular genetics, and stress ecology.

The advantages of this review over similar existing publications include:

The work’s primary conceptual strength lies in substantiating the thesis that abiotic stress resilience is achieved not through maximal cell wall strengthening, but through the ability to precisely modulate wall stiffness in both time and space. This shifts the focus of future research from identifying "strength-related candidate genes" to investigating the mechanisms of adaptive relaxation.
The authors convincingly demonstrate the bidirectional nature of this relationship: not only do hormones (ABA, auxin, ethylene, brassinosteroids) regulate the cell wall state via expansins, XTHs, and PMEs, but CWI receptors (primarily FERONIA and THE1) also directly modulate phytohormone synthesis. 3. The review effectively highlights the fundamental distinction between Type I (Arabidopsis) and Type II (grass) cell walls. The authors rightly point out that extrapolating data from Arabidopsis to wheat or maize (e.g., regarding pectin methylation) requires caution, and they emphasize processes specific to grasses (GAX feruloylation, mixed-linkage glucan metabolism). This is critically important for translational biology.
Emphasis on feedback loops (CWI-hormone signaling). The mechanisms by which disrupted cellulose synthesis triggers compensatory lignification and jasmonate accumulation (via the SCOOP18-MIK2 module) are analyzed in detail, linking structural integrity to immunity and stress responses.

Shortcomings and observations:

Insufficient detail regarding cell wall type differences. Section 2.1 mentions the differences between grass and dicot cell walls; however, in subsequent sections (especially when discussing drought and salt stress), mechanisms are often described in generalized terms. Where possible, it would be better to specify which mechanisms (e.g., pectin demethylesterification) are universal and which are specific to certain wall types and cannot be directly extrapolated to cereal crops.
Integration of multi-omics and mechanobiology data. While the text asserts the importance of spatial multi-omics, the presented section lacks concrete examples of successfully linking ATAC-seq or spatial transcriptomics data with direct Young's modulus measurements in the same tissues.
Latin plant names are not italicized. More than half of the cited references are from the last five years.

The figures and tables are easy to interpret and clearly illustrate the complexity of the system.

Specialized reviews focusing on individual hormones (e.g., solely on ABA or brassinosteroids) or exclusively on cell wall composition are published regularly. However, this review offers significant novelty precisely because of its integrative approach. Most recent publications address either signaling pathways or cell wall structure. By linking mechanosensing with multi-hormonal networks in the context of climate change, this work fills an important gap and is of great interest to the scientific community, as it proposes a ready-made conceptual model for future research.

The review is exceptionally clear in its presentation. The authors have successfully synthesized data from polymer biochemistry, mechanobiology, molecular genetics, and stress physiology into a unified conceptual framework. The review is highly timely, as it shifts the focus from the classical view of "wall strengthening for protection" to the concept of "dynamic plasticity"—a cutting-edge area in plant science.

The article will appeal to a broad audience beyond a narrow specialization. The mechanisms of hormonal-mechanical integration represent a universal topic relevant to anyone studying plant adaptation to the environment.

The review demonstrates high scientific novelty and aligns perfectly with the journal's scope; it is recommended for publication in a peer-reviewed scientific journal, subject to addressing minor comments.

Author Response

Response to Reviewer 3 Comments

Dear Reviewer,

We sincerely thank the reviewer for their thorough and constructive evaluation of our manuscript. Their insightful comments and suggestions have substantially strengthened the scientific depth, clarity, and overall presentation of our work, and we are grateful for the time and expertise they have invested in this review. We have carefully considered each comment and revised the manuscript, accordingly, as detailed in our point-by-point responses below. For ease of evaluation, all changes made in response to Reviewer 3's comments are highlighted in Purple color, in the revised manuscript. We believe these revisions have significantly improved the manuscript, and we hope it now meets the standards for publication in Biomolecules.

General Comments

Comment 1. This review addresses a fundamental and highly relevant issue in modern plant physiology: the integration of hormonal signals and the mechanical state of the cell wall (CWI) in the context of global climate change. The authors successfully move beyond the traditional paradigm—which views the cell wall merely as a passive scaffold to present it instead as a dynamic sensory-signaling matrix. The manuscript follows a logical progression: starting with the basic composition of polymers and remodeling enzymes, moving to cell wall integrity (CWI) control systems and complex phytohormone interaction networks, and concluding with applied aspects of crop breeding. Unlike existing reviews that focus either exclusively on polysaccharide biochemistry or on specific hormonal pathways, this work employs a profound systems-level approach that integrates biomechanics, molecular genetics, and stress ecology.

Response: We sincerely thank the reviewer for this thoughtful and encouraging evaluation of our manuscript. We greatly appreciate the recognition of the review’s integrative perspective, particularly its effort to connect cell wall composition and remodeling, cell wall integrity (CWI) signaling, phytohormone crosstalk, environmental stress responses, and crop improvement within a unified framework. One of the main objectives of this review was to move beyond the traditional perception of the plant cell wall as a passive structural component and instead highlight its dynamic role as a sensory and signaling interface that interacts closely with hormonal networks under changing environmental conditions. We are particularly grateful that the reviewer recognizes the systems-level approach of the manuscript and its integration of biomechanics, molecular genetics, and stress ecology. We have carefully maintained and further strengthened this conceptual framework throughout the revised manuscript, with particular emphasis on the relevance of hormone cell wall interactions for plant adaptation and climate-resilient crop breeding. We sincerely appreciate the reviewer’s positive comments and valuable assessment of our work.

Comment 2. The advantages of this review over similar existing publications include:

The work’s primary conceptual strength lies in substantiating the thesis that abiotic stress resilience is achieved not through maximal cell wall strengthening, but through the ability to precisely modulate wall stiffness in both time and space. This shifts the focus of future research from identifying "strength-related candidate genes" to investigating the mechanisms of adaptive relaxation.

Response: We sincerely thank the reviewer for highlighting this important conceptual strength of our review. We agree that stress resilience should not be interpreted simply as increased cell wall strengthening, but rather as the capacity of plants to dynamically and precisely adjust wall stiffness according to developmental stage, tissue type, and environmental conditions. In the revised manuscript, we have further emphasized this concept by clarifying that successful adaptation depends on a balance between wall reinforcement and controlled wall relaxation. We also strengthened the discussion on how hormonal signaling and cell wall integrity pathways coordinate these spatially and temporally regulated changes. This perspective broadens the focus beyond the identification of genes associated solely with wall strengthening and highlights adaptive wall remodeling and relaxation as important targets for future mechanistic studies and crop improvement.

Comment 3. The authors convincingly demonstrate the bidirectional nature of this relationship: not only do hormones (ABA, auxin, ethylene, brassinosteroids) regulate the cell wall state via expansins, XTHs, and PMEs, but CWI receptors (primarily FERONIA and THE1) also directly modulate phytohormone synthesis.

Response: We sincerely thank the reviewer for recognizing the bidirectional nature of hormone–cell wall integrity (CWI) interactions highlighted in our review. We agree that this reciprocal regulation is central to understanding how plants coordinate growth and stress adaptation. In the revised manuscript, we have further clarified that phytohormones such as ABA, auxin, ethylene, and brassinosteroids regulate cell wall properties through remodeling proteins and enzymes, including expansins, XTHs, and PMEs. At the same time, CWI-associated receptors such as FERONIA (FER) and THESEUS1 (THE1) perceive changes in cell wall status and feed this information back into hormonal signaling and biosynthetic pathways. We have strengthened this discussion to emphasize that the cell wall and hormonal networks function as an integrated feedback system rather than as a simple one-way regulatory pathway.

Comment 4. The review effectively highlights the fundamental distinction between Type I (Arabidopsis) and Type II (grass) cell walls. The authors rightly point out that extrapolating data from Arabidopsis to wheat or maize (e.g., regarding pectin methylation) requires caution, and they emphasize processes specific to grasses (GAX feruloylation, mixed-linkage glucan metabolism). This is critically important for translational biology.

Response: We thank the reviewer for this positive assessment and for emphasizing the translational importance of distinguishing Type I and Type II cell walls. We agree that differences in wall composition and architecture can influence the contribution of individual remodeling processes to stress adaptation. Accordingly, we emphasize caution when extrapolating pectin- and xyloglucan-centered mechanisms established in Arabidopsis to cereal crops such as wheat and maize. We also highlight grass-specific processes, including GAX substitution and feruloylation, mixed-linkage glucan metabolism, and xylan-lignin interactions. This distinction helps frame Arabidopsis findings as mechanistic guides that require validation in the relevant crop, tissue, and stress context.

Comment 5. Emphasis on feedback loops (CWI-hormone signaling). The mechanisms by which disrupted cellulose synthesis triggers compensatory lignification and jasmonate accumulation (via the SCOOP18-MIK2 module) are analyzed in detail, linking structural integrity to immunity and stress responses.

Response: We thank the reviewer for recognizing the importance of feedback between CWI and hormone signaling. We agree that cellulose disruption provides a valuable example of how structural perturbations activate compensatory and defense-related responses. Our discussion highlights the SCOOP18-MIK2 module in wall-damage-induced lignification and immunity potentiation, alongside evidence for MIK2-dependent jasmonate accumulation following cellulose-biosynthesis inhibition. These findings illustrate how wall integrity is functionally connected to hormonal regulation, growth adjustment, and immunity. We also distinguish these experimentally supported responses from broader proposed roles under abiotic stress, where further mechanistic validation remains necessary.

Shortcomings and observations:

Comment 1. Insufficient detail regarding cell wall type differences. Section 2.1 mentions the differences between grass and dicot cell walls; however, in subsequent sections (especially when discussing drought and salt stress), mechanisms are often described in generalized terms. Where possible, it would be better to specify which mechanisms (e.g., pectin demethylesterification) are universal and which are specific to certain wall types and cannot be directly extrapolated to cereal crops.

Response: We thank the reviewer for this valuable comment. We have revised Sections 2.1, 6.1, and 6.2 to better distinguish broadly conserved wall processes from wall-type-specific mechanisms. We now clarify that pectin- and xyloglucan-centered mechanisms are mainly established in Type I walls, whereas cereal Type II walls require greater consideration of GAX feruloylation, mixed-linkage glucans, xylan cross-linking, and lignification. These revisions reduce overgeneralization and improve the relevance of the review to cereal crops.

Comment 2. Integration of multi-omics and mechanobiology data. While the text asserts the importance of spatial multi-omics, the presented section lacks concrete examples of successfully linking ATAC-seq or spatial transcriptomics data with direct Young's modulus measurements in the same tissues.

Response: We thank the reviewer for this helpful observation. We agree that the section would be stronger with concrete examples linking spatial molecular data to direct measurements of wall mechanics. We do not provide a verified study combining ATAC-seq or spatial transcriptomics with Young’s modulus measurements in the same tissues, so we describe this integration as a future research priority. A useful approach would be to pair spatial profiling with localized AFM measurements in the same tissue, developmental stage, and stress treatment. We also emphasize that gene expression and chromatin accessibility can help identify candidate pathways, but direct mechanical measurements are needed to establish their effects on the wall.

Comment 3. Latin plant names are not italicized. More than half of the cited references are from the last five years.

Response: We thank the reviewer for noting these points. Latin genus and species names should be italicized consistently throughout the manuscript, including tables and figure captions. We also appreciate the reviewer’s observation that more than half of the references were published within the last five years. These recent studies help reflect current advances, while older foundational references provide essential context for established mechanisms.

General comments: The figures and tables are easy to interpret and clearly illustrate the complexity of the system.

Response: We thank the reviewer for these encouraging comments. We are glad that the figures and tables make this complex topic easier to follow. Our goal is to bring together research on cell-wall structure, remodeling, mechanosensing, and hormone signaling to show how these processes interact during abiotic stress. We appreciate the reviewer’s recognition of this approach and its relevance to climate-related challenges. We hope the framework provides a useful starting point for future studies linking molecular mechanisms with changes in wall properties and, ultimately, crop performance.

General comments: The review is exceptionally clear in its presentation. The authors have successfully synthesized data from polymer biochemistry, mechanobiology, molecular genetics, and stress physiology into a unified conceptual framework. The review is highly timely, as it shifts the focus from the classical view of "wall strengthening for protection" to the concept of "dynamic plasticity"—a cutting-edge area in plant science.

Response: We thank the reviewer for these thoughtful and encouraging comments. We aimed to bring together research from several fields to explain how hormone signaling and cell-wall changes contribute to plant adaptation. We are glad that the focus on dynamic wall plasticity is clear, especially the importance of remodeling walls in the right tissue and at the right time. We also appreciate the reviewer’s view that the review will interest a broad readership. We hope it provides a useful basis for further research across hormone signaling, cell-wall biology, and stress physiology.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed the queries to satisfactory level

Reviewer 2 Report

Comments and Suggestions for Authors

Following the substantial revisions made to the manuscript, I believe that it is now suitable for publication in Biomolecules.