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Sculpting Organs: Mechanical Regulation of Tissue Development
Abstract
The ramified architectures of organs such as the mammary gland and lung are generated via branching morphogenesis, a developmental process through which individual cells bud and pinch off of pre-existing epithelial sheets. Although specified by signaling programs, organ development requires integration of all aspects of the microenvironment. We describe the essential role of endogenous cellular contractility in the formation of branching tubes. We also highlight the role of exogenous forces in normal and aberrant branching.
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“Finally, it has become increasingly clear that the mechanical properties in three-dimensional (3D) culture systems can have large effects on cell51, organoid52, tissue53, and organ development54,55.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [53]
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BackgroundThe Extracellular, Cellular, and Nuclear Stiffness, a Trinity in the Cancer Resistome—A Review
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Self-induced mechanical stress can trigger biofilm formation in uropathogenic Escherichia coli
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BackgroundHyaluronan modulates growth factor induced mammary gland branching in a size dependent manner
Tölg, C., Yuan, H., Flynn, S. M., Basu, K., Ma, J., Tse, K. C. K., Kowalska, B., Vulkanesku, D., Cowman, M. K., McCarthy, J. B., et al. (2017) · Matrix Biology · doi:10.1016/j.matbio.2017.02.003 · Cited by 59
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Self-citationMorphomechanics: transforming tubes into organs
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“…epithelial cell–cell adhesions creates critical cell subpopulations during morphogenesis Branching morphogenesis and the establishment of mature organ structure require complex spatio-temporal regulation of cell–cell adhesions (Hsu and Yamada, 2010; Nelson and Gleghorn, 2012; Walker et al., 2008).”
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“Similar actin sheets with embedded signaling complexes linked to undulating cellular interfaces should play a comparably important role whenever dynamic cell contacts drive cell fate decisions, such as in development [36], stem differentiation [37], and cancer metastasis [38].”
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“The evolving tissue architecture: a kinematic understanding The architecture of a tissue is linked to its function [1,2,3 ].”
Self-citationOlutoye, O. O., Short, W. D., Gilley, J., Hammond, J. D., Belfort, M. A., Lee, T. C., King, A., Espinoza, J., Joyeux, L., Lingappan, K., et al. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.925106 · Cited by 16
Self-citationLet's push things forward: disruptive technologies and the mechanics of tissue assembly
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Self-citationThe development of body and organ shape
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The Mechanics of Building Functional OrgansPreprint
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“…to the forces it experiences; from the behaviour of its constituent cells, neighbouring tissues, and the dynamic environment it is growing in (Nelson and Gleghorn 2012; Stooke-Vaughan and Campas 2018; Trepat and Sahai 2018; Hannezo and Heisenberg 2019; Hamant and Saunders 2020; Collinet and…”
Effects of Elasticity on Cell Proliferation in a Tissue-Engineering Scaffold Pore
Annunziata, C., Fattahpour, H., Fong, D., Hadjiargyrou, M., & Sanaei, P. (2023) · Bulletin of Mathematical Biology · doi:10.1007/s11538-023-01134-7 · Cited by 14
“Additionally, the engineered scaffoldmust offer a suitable microenvironment (i.e., ideal substrate and material properties), which will facilitate cell adhesion followed by robust proliferation (Nelson and Gleghorn 2012; Barthes et al. 2014; Engler et al. 2006; Lee-Thedieck and Spatz 2014).”
BackgroundPiotrowski-Daspit, A. S., Simi, A. K., Pang, M.-F., Tien, J., & Nelson, C. M. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6475-8_12 · Cited by 14
Self-citationAndrews, T. G. R., Cornwall-Scoones, J., Ramel, M., Gupta, K., Briscoe, J., & Priya, R. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.07.011 · Cited by 15
Gilbert, R. M., & Gleghorn, J. P. (2023) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00349.2022 · Cited by 13
Self-citationLi, J., Zhang, W., Liu, A., Lu, Y., Yu, L., Liu, X., Sun, L., Zhao, B., Tong, X., Liu, T., et al. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202401564 · Cited by 13
Donzanti, M. J., Ferrick, B. J., Mhatre, O., Chernokal, B., Renteria, D. C., & Gleghorn, J. P. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.4c01247 · Cited by 13
Self-citationNegative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
Stanton, A. E., Goodwin, K., Sundarakrishnan, A., Jaslove, J. M., Gleghorn, J. P., Pavlovich, A. L., & Nelson, C. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.725785 · Cited by 12
“In addition to these biochemical signals, the embryonic lung is exposed to a variety of mechanical forces (Nelson and Gleghorn, 2012; Hogan, 2018).”
BackgroundSelf-citationAhmed, D. W., Eiken, M. K., DePalma, S. J., Helms, A. S., Zemans, R. L., Spence, J. R., Baker, B. M., & Loebel, C. (2023) · iScience · doi:10.1016/j.isci.2023.108472 · Cited by 10
Focal sources of FGF-10 promote the buckling morphogenesis of the embryonic airway epithelium
Peak, K. E., Mohr-Allen, S. R., Gleghorn, J. P., & Varner, V. D. (2022) · Biology Open · doi:10.1242/bio.059436 · Cited by 11
Self-citationChernokal, B., Ferrick, B. J., & Gleghorn, J. P. (2024) · Lab on a Chip · doi:10.1039/d4lc00579a · Cited by 10
Self-citationManipulating the Patterns of Mechanical Forces That Shape Multicellular Tissues
Herrera-Perez, R. M., & Kasza, K. E. (2019) · Physiology · doi:10.1152/physiol.00018.2019 · Cited by 10
Mastering Organoid Growth: A Complete Guide to Overcoming Methodological Challenges
Jiao, C., Karakaya, O. F., Dadgar, N., Wehrle, C. J., Massoud, Z., Hong, H., Fairchild, R. L., Leipzig, N. D., Aucejo, F., Ma, W. W., et al. (2026) · MedComm · doi:10.1002/mco2.70571 · Cited by 9
A Systems Approach to Biomechanics, Mechanobiology, and Biotransport
Peirce, S. M., Sander, E. A., Fisher, M. B., Deymier, A. C., LaDisa, J. F., O’Connell, G. D., Corr, D. T., Han, B., Singh, A. K., Wilson, S. E., et al. (2024) · Journal of Biomechanical Engineering · doi:10.1115/1.4064547 · Cited by 6
Fiaz, A. W., Léon‐Kloosterziel, K. M., LEEUWEN, J. L. V., & Kranenbarg, S. (2014) · Journal of Applied Ichthyology · doi:10.1111/jai.12510 · Cited by 6
Nelson, C. M. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.09.014 · Cited by 6
“The past 10 years have thus seen a resurgent interest in the ideas of Thompson, Wilhelm His, and other early developmental biologists and renewed efforts to investigate the mechanical mechanisms that underlie tissue morphogenesis (Nelson and Gleghorn, 2012).”
BackgroundSelf-citationMechanobiology throughout development
Gleghorn, J. P., & Killian, M. L. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812952-4.00003-9 · Cited by 6
Self-citationNimiritsky, P., Novoseletskaya, E. S., Eremichev, R. Y., Alexandrushkina, N. A., Karagyaur, M. N., Vetrovoy, O. V., Basalova, N. A., Khrustaleva, A. M., Tyakht, A., Efimenko, A. Y., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9091192 · Cited by 6
“As mentioned before, Rho GTPase pathway via ROCK-1/2 activity governs rearrangement of actin cytoskeleton during mesenchymal condensation preceding organogenesis in vivo [96].”
BackgroundGonyea, C. R., Shen, Y., Nelson, K. M., Bird, R. N., Gilbert, R. M., Olutoye, O. O., Keswani, S. G., & Gleghorn, J. P. (2025) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00233.2024 · Cited by 5
Self-citationSymmetry breaking during morphogenesis in the embryo and in engineered tissues
Nelson, C. M. (2012) · AIChE Journal · doi:10.1002/aic.13941 · Cited by 5
Self-citationMiyake, Y., Tse, W. H., Wang, J. Q., Leon, N. D., Mourin, M., Patel, D., Aptekmann, A. O., Yamataka, A., & Keijzer, R. (2022) · Pediatric Surgery International · doi:10.1007/s00383-022-05340-7 · Cited by 5
“Fetal lung fluid and fetal breathing movements cause bio-mechanical forces on the fetal lung, which play an important role in fetal lung development [12].”
Early Development of the Mammalian Lung-Branching Morphogenesis
Stewart, K. M., & Morrisey, E. E. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781139680349.003 · Cited by 5
Mechanics of the cellular microenvironment as perceived by cells in vivoPreprint
Mongera, A., Pochitaloff, M., Gustafson, H. J., Stooke‐Vaughan, G. A., Rowghanian, P., & Campàs, O. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.04.425259 · Cited by 5
Peak, K. E., Rajaguru, P., Khan, A. R., Gleghorn, J. P., Obaid, G., Ferruzzi, J., & Varner, V. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.22.609268 · Cited by 5
Self-citationForce-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets
Scholp, A. J., Jensen, J., Chinnathambi, S., Atluri, K., Mendenhall, A., Fowler, T. P., Salem, A. K., Martin, J. A., & Sander, E. A. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.907611 · Cited by 4
Mechanical Cues Regulate Cargo Sorting and Export at the Golgi
Serafino, G., Forciniti, S., Scarpa, E., Ranieri, A., Santorelli, L., Blasi, G. D., Costantini, S., Lee, E. H., Galeone, A., Calcagnì, A., et al. (2025) · Advanced Science · doi:10.1002/advs.202506241 · Cited by 3
Developmental Biology-Based 3D Bioprinting: An Off-the-Shelf Strategy to Induce Tissue Regeneration
Chakraborty, J., & Ghosh, S. (2025) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5c00213 · Cited by 4
Purkayastha, P., Pendyala, K., Saxena, A. S., Hakimjavadi, H., Chamala, S., Dixit, P. D., Baer, C. F., & Lele, T. P. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab102 · Cited by 3
“This differential proliferation results in elongated and laterally branched structures (Gjorevski and Nelson 2011; Nelson and Gleghorn 2012).”
Background
Metadata
- Authors
- Nelson, C. M., & Gleghorn, J. P.
- Affiliations
- Princeton University (US)
- Department of Chemical and Biological Engineering and
- Venue
- Annual Review of Biomedical Engineering
- Publisher
- Annual Reviews
- Published
- 2012-08-15
- Volume
- 14
- Issue
- 1
- Pages
- 129-154
- ISSN
- 1523-9829 (ISSN-L)
- 1545-4274
- OpenAlex
- W2170979166
- Cited by
- 130
- References
- 189
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 7 · 2017: 12 · 2016: 11 · 2015: 4 · 2014: 12 · 2013: 10 · 2012: 3
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Burroughs Wellcome Fund
- Susan G. Komen
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R21HL110335, HL110335)
- National Cancer Institute (CA128660, R21CA128660)
- National Institute of General Medical Sciences (R01GM083997, GM083997)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- branching morphogenesis, organogenesis, cell contractility, mechanical regulation, mammary gland, lung development, epithelial sheets, microenvironment, tissue mechanics
- MeSH terms
- Animals, Biomedical Engineering, Humans, Lung, Mammary Glands, Animal, Models, Genetic, Morphogenesis, Time Factors, Signal Transduction, Gene Expression Regulation, Developmental, Tissue Engineering, Organogenesis, Mammary Glands, Human
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