Open research questions in Cellular Mechanics and Interactions
158 unresolved questions extracted from the limitations and future-work sections of 414 Cellular Mechanics and Interactions papers in our library. Each links back to the study that raised it.
What the literature leaves open
Network models have established a rigorous framework linking microscopic architecture to macroscopic tissue mechanics, successfully predicting mechanical and structural properties of reconstituted cytoskeletal and ECM networks. Translating these insights to living tissues raises five open ques- tions. First, chemo-mechanical coupling: physiological networks turnover on time scales of seconds to minutes, driven by force-sensitive signaling. Agent-based simulations already couple local stress to reaction-diffusion kinetics at the single-network scale, most directly in MEDYAN71 and with force-sensitive binding kinetics in AFINES39 and Cytosim72. Scaling this coupling to tissues, and integrating it with the continuum descriptions discussed next, remain open. Second, multiscale integration: cell-generated forces deform the ECM, which feeds back on cells through mechan- osensitive adhesions, requiring hybrid schemes that couple discrete fiber models to continuum descriptions within a unifying framework that is currently lacking. Third, structural heterogeneity: most models assume isotropy, but pathological tissues—fibrotic lung, desmoplastic stroma, atherosclerotic plaque—are defined by local architectural defects, placing npj Biological Physics and Mechanics | (2026) 3:16 5 https://doi.org/10.1038/s44341-026-00045-7
The study faced challenges in terms of heterogeneity among included studies. The study also faced challenges in terms of publication bias and the quality of included studies. Additionally, the study had limited data on long-term survival outcomes.
Efficacy and safety of thymosin α1 combined with chemotherapy for gastric cancer: a systematic review and meta-analysis of randomized controlled trials · 2026 · DOILack of long-term survival data, - High heterogeneity among studies for some outcomes, - Limited information on appropriate patient population for thymosin α1 combined with chemotherapy, - Limited information on optimal dosing regimen
Efficacy and safety of thymosin α1 combined with chemotherapy for gastric cancer: a systematic review and meta-analysis of randomized controlled trials · 2026 · DOIThe model does not include steric effects, - The model is a simplification of the complex process of cell polarization, - The model is based on a discrete active network, - The model does not account for external cues or complex signaling networks, - The model is limited to a 2D representation
Balanced contractility and adhesion drive polarization in a minimal elastic actomyosin network · 2026 · DOIInvestigating the effects of external cues on the system, - Examining the role of complex signaling networks in cell polarization, - Developing a more comprehensive model that includes steric effects and other complexities, - Exploring the application of the model to different cell types and biological processes
Balanced contractility and adhesion drive polarization in a minimal elastic actomyosin network · 2026 · DOIYet, how this attachment shapes concurrent global morphogenetic events remains unclear.
Multiple contact sites between cells and the vitelline envelope coordinate tissue flows in Drosophila gastrulation · 2026 · DOIAlthough EM cells migrate directionally toward wounds, how they navigate through unwounded tissues during early colonization remains unclear.
Tissue flow acts as a guidance cue for immune cell polarization and directional migration · 2026 · DOIExtensive experimental evidence suggests that particle shape strongly influences the phagocytosis rate and immune cell targeting, showing disparate and cell-dependent trends that remain poorly understood.
Cell-Dependent Particle Shape Preference during Phagocytosis is Governed by Cell Mechanics · 2026 · DOIThe mechanisms by which epithelial stem cells (SCs) sense mechanical cues within their niche and convert the information into biochemical signals to govern their function are not well understood.
PIEZO1-mediated calcium signaling reinforces mechanical properties of hair follicle stem cells to promote quiescence · 2025 · DOIHowever, the interplay between matrix degradability and mechanical properties remains underexplored.
While chemical interactions among immune cells play a prominent role in the immune response, the manner in which physical factors, such as mechanical forces, shape the behaviors and functions of immune cells remains inadequately understood.
Mechanotransduction in Shaping Immunity: Pathways, Crosstalk, and Pathophysiological Relevance · 2025 · DOIThe contribution of BMP receptors in defining tip-cell characteristics is poorly understood.
Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling · 2025 · DOIHowever, as a main regulator of cell morphology and function, whether the extracellular osmolarity change may affect osteoblast migration remains unclear.
Extracellular osmolarity regulates osteoblast migration through the TRPV4-Rho/ROCK signaling · 2025 · DOICalponin (CNN) family proteins are abundant stress fiber components, but their cellular functions and isoform-specific roles remain poorly understood.
Calponin isoforms define the cell-type-specific organization and dynamics of actomyosin bundles · 2025 · DOIHowever, little is known about how cisplatin resistance (CR) alters the biophysical properties of EOC multicellular aggregates and how this impacts metastasis.
Cisplatin resistance alters ovarian cancer spheroid formation and impacts peritoneal invasion · 2025 · DOIThe underlying design principles and mechanisms governing this collective behavior remain poorly understood.
Despite their importance, how these structures are organized during T-cell development remains unclear, and their functions are still not fully understood.
A reporter assay revealed that the promoter region alone was insufficient for Coro1a transcription; both the promoter and gene body regions were required.
However, the regulatory mechanisms of Coro1a expression in immune cells remain unknown.
However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime.
Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing · 2024 · DOIHowever, the relation of nuclear deformation and migration dynamics in confinement remains unclear.
Nuclear deformation and dynamics of migrating cells in 3D confinement reveal adaptation of pulling and pushing forces · 2024 · DOIRelatively little is known about how the viscoelastic properties of the substrate impact NSC fate commitment.
" The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood.
A minimal physical model for curvotaxis driven by curved protein complexes at the cell’s leading edge · 2024 · DOIIt remains unclear how the motility machinery of confined cells responds and adapts to their microenvironment.
While it has been shown that hexatic order in tissue models can be induced by motility and thermal fluctuations, the role of cell division and apoptosis (birth and death) has remained poorly understood, despite its fundamental biological role.
Most-cited papers in Cellular Mechanics and Interactions
- Tissue Cells Feel and Respond to the Stiffness of Their Substrate · Science · 2005 · 5,769 citations
- Rho GTPases and the Actin Cytoskeleton · Science · 1998 · 5,146 citations
- Cell Migration: Integrating Signals from Front to Back · Science · 2003 · 4,194 citations
- Regulated portals of entry into the cell · Nature · 2003 · 3,238 citations
- Reversible Unfolding of Individual Titin Immunoglobulin Domains by AFM · Science · 1997 · 2,802 citations
- Cell mechanics and the cytoskeleton · Nature · 2010 · 2,792 citations
- Taking Cell-Matrix Adhesions to the Third Dimension · Science · 2001 · 2,558 citations
- Mechanotransduction Across the Cell Surface and Through the Cytoskeleton · Science · 1993 · 2,482 citations
- Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis · Nature Cell Biology · 2023 · 1,049 citations
- Mechanical regulation of bone remodeling · Bone Research · 2022 · 598 citations
Most recent work
- Optimal mechanical noise ensures robust vertebrate body segmentation · bioRxiv · 2026
- Development and Characterization of 50 nanometer diameter Genetically Encoded Multimeric Nanoparticles · bioRxiv · 2026
- Establishing functional giant Dictyostelium cells reveals front–rear polarity in intracellular signaling · Communications Biology · 2026
- Mechanosensitive Remodeling Sustains Rigidity Homeostasis and Elastic Memory in Actin Cortex Models · bioRxiv · 2026
- Extracellular matrix mediated stresses spatially bias myoblast fusion and myotube growth · bioRxiv · 2026
- 3D confinement physically regulates cell cycle progression in budding yeast · bioRxiv · 2026
- Mechanism of actin thin filament pointed-end elongation by leiomodin · Nature Communications · 2026
- Adhesion-driven rigidity transition decoupled from density-driven jamming triggers epithelial organization in embryonic tissues · Nature Physics · 2026
- Spatio-temporal Force Patterns Reveal a Mechanical Set Point in Early T Cell Activation · bioRxiv · 2026
- Intracellular mechanical fingerprint reveals cell type-specific mechanical differences · bioRxiv · 2026
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