From Force to Function: Nuclear Mechanobiology in Health and Disease

Nuclear mechanobiology sits at the intersection of biophysics, cell biology, and disease research, probing how mechanical forces are transmitted from the cellular microenvironment into the nucleus and translated into cellular responses. Recent advances in live-cell imaging, force sensor technologies, and single-cell multi-omics have allowed unprecedented insight into the dynamic behavior of nuclear structures such as the lamina, chromatin, and nuclear pores in response to physical cues. These discoveries are shedding light on the underlying mechanisms by which nuclear deformation, chromatin topology changes, and force-induced alterations in transcriptional machinery impact cell fate decisions. Notably, there remain substantial questions about how distinct mechanical inputs—such as stress, confinement, or matrix mechanics—specifically influence gene programs and how dysregulation of these processes contributes to diseases ranging from cancer and cardiovascular disorders to laminopathies and age-related degeneration.

Despite these recent breakthroughs, critical gaps remain in our understanding of the quantitative principles and predictive models governing nuclear mechanotransduction and its outcomes at the genomic, cellular, and tissue levels. Major ongoing debates concern the causal links between mechanical signals and gene expression changes: What are the precise pathways and feedbacks through which nuclear mechanics orchestrates epigenomic modifications, transcriptional bursting, or enhancer–promoter interactions? While it is widely recognized that nuclear mechanical defects can drive genome instability and aberrant cell fate, the disease-specific mechanisms and potential for clinical intervention remain underexplored. There is thus a pressing need for studies that integrate biophysical quantification, mechanistic perturbations, and multi-scale computational modeling to provide a holistic view of nuclear mechanobiology.

This Research Topic aims to unite groundbreaking work that delineates how nuclear mechanics influences genomic regulation, phenotype, and disease progression. We seek contributions that leverage quantitative approaches—from advanced imaging, mechanical probing, and mechanogenomics pipelines to innovative computational and theoretical frameworks—to map causal chains between defined mechanical cues, nuclear architectural changes, chromatin organization, gene regulatory networks, and cellular functions. Submissions should illuminate key questions: How do forces reach and reshape the nucleus? Which nuclear structures mediate signal integration and memory? How do these pathways break down during disease? and what points of intervention are most promising for therapeutic innovation?

The scope encompasses original research, reviews, and methods that explicitly connect mechanical signals to nuclear outcomes and gene-regulatory consequences in both physiological and pathological contexts. Purely descriptive or correlative studies lacking biomechanical variables or nuclear/genomic readouts fall outside this focus. We encourage work with quantitative rigor, causal perturbations, and transparent, reproducible practices. To gather further insights into the mechanisms and roles of nuclear mechanobiology in health and disease, we welcome articles addressing, but not limited to, the following themes:

Transmission of mechanical forces to and within the nucleus (e.g., LINC complex, lamina, perinuclear cytoskeleton)

Mechanosensitive regulation of nuclear pores, chromatin architecture, and phase-separated condensates

Force-dependent chromatin remodeling, transcriptional bursting, and epigenetic memory

Genome stability, nuclear rupture, and DNA damage repair under mechanical stress

Mechanically driven differentiation, inflammation, aging, and disease models (cancer, fibrosis, cardiovascular, rare nuclear diseases)

Development and benchmarking of new biophysical tools, live-cell force sensors, and mechanogenomics platforms

Multiscale computational models linking mechanical input to nuclear and genomic outputs

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy Brief
• Review
• Systematic Review
• Technology and Code

Keywords: Nuclear mechanobiology, mechanotransduction, chromatin architecture, LINC complex/lamina, mechanogenomics, genome stability, disease models.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.