Journal article
Extracellular matrix physical properties regulate cancer cell morphological transitions in 3D hydrogel microtissues
Acta biomaterialia, v 210, pp 17-26
01 Jan 2026
PMID: 41352623
Abstract
Solid tumor cells can adopt a range of morphological states linked to distinct functional behaviors during tumor progression. Some remain in a proliferative state, forming tight clusters, others detach and elongate into an invasive state, and some retain a rounded amoeboid form with minimal matrix adhesion. However, factors determining which morphological state a cell adopts remain poorly understood. We used a combined theoretical and experimental framework to study how extracellular matrix (ECM) mechanics regulate solid tumor cell morphology in three-dimensional (3D) environments. We developed a theoretical mechanical energy model based on the minimum energy principle, which suggests that a cell will adopt the morphological state (rounded, elongated, or clustered) that minimizes the total energy of the cell-ECM system. Using MDA-MB-231 breast cancer cells, we established a reliable protocol for encapsulating cells into 3D naturally-derived hydrogels with controlled stiffness. We confirmed the model’s results in vitro over an extended culture period. In soft ECMs, cells transitioned over time to an elongated morphology, while in stiff ECMs, cells favored clustered configurations. These transitions were governed by the hydrogel-based ECM’s physical, not chemical, properties, as confirmed using chemically distinct yet mechanically matched composite matrices. These new insights have implications for solid tumor cell invasion modeling in vitro.
We study the fundamental question of how solid tumor cells adapt their morphology in response to the physical characteristics of the extracellular matrix. This work establishes a robust experimental platform for studying cellular markers in triple-negative breast cancer (TNBC) cells, followed by a biophysical modeling of the cell invasion. Cell clustering was observed in stiffe ECMs, while an elongated morphology was observed in soft ECMs. Our theoretical modeling revealed how the biophysical properties of the matrix can impact cell morphology and invasion behavior. This work can contribute to personalized medicine by making more effective, tailored cancer models.
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- Title
- Extracellular matrix physical properties regulate cancer cell morphological transitions in 3D hydrogel microtissues
- Creators
- Ayda Pourmostafa - New Jersey Institute of TechnologyGabrielle Uskach - New Jersey Institute of TechnologyMohammad Jafari - New Jersey Institute of TechnologyElvan Dogan - Drexel UniversitySwaprakash Yogeshwaran - New Jersey Institute of TechnologyTeresa L. Wood - Rutgers, The State University of New JerseySobhan Ghaeini-Hesaroueiye - School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USALin Han - Drexel University, School of Biomedical Engineering, Science, and Health SystemsFarid Alisafaei - New Jersey Institute of TechnologyAmir K. Miri - New Jersey Institute of Technology
- Publication Details
- Acta biomaterialia, v 210, pp 17-26
- Publisher
- Elsevier Inc
- Number of pages
- 10
- Grant note
- NJITNational Institute Of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health: R01AR084243
The authors gratefully acknowledge NJIT funding. A.K.M. acknowledges the financial support from NSF-2243506 and NSF-2426919 grants for this work. F.A. acknowledges the support by the National Institute Of Arthritis And Musculoskeletal And Skin Diseases of the National Institutes of Health under Award Number R01AR084243. The content is solely the responsibility of the authors and does not neces-sarily represent the official views of the National Institutes of Health or the National Science Foundation.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001668939600001
- Scopus ID
- 2-s2.0-105027287115
- Other Identifier
- 991022138582804721