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Stress generation, relaxation and size control in confined tumor growth
- Source :
- PLoS Computational Biology, Vol 17, Iss 12, p e1009701 (2021), PLoS Computational Biology
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
Abstract
- Experiments on tumor spheroids have shown that compressive stress from their environment can reversibly decrease tumor expansion rates and final sizes. Stress release experiments show that nonuniform anisotropic elastic stresses can be distributed throughout. The elastic stresses are maintained by structural proteins and adhesive molecules, and can be actively relaxed by a variety of biophysical processes. In this paper, we present a new continuum model to investigate how the growth-induced elastic stresses and active stress relaxation, in conjunction with cell size control feedback machinery, regulate the cell density and stress distributions within growing tumors as well as the tumor sizes in the presence of external physical confinement and gradients of growth-promoting chemical fields. We introduce an adaptive reference map that relates the current position with the reference position but adapts to the current position in the Eulerian frame (lab coordinates) via relaxation. This type of stress relaxation is similar to but simpler than the classical Maxwell model of viscoelasticity in its formulation. By fitting the model to experimental data from two independent studies of tumor spheroid growth and their cell density distributions, treating the tumors as incompressible, neo-Hookean elastic materials, we find that the rates of stress relaxation of tumor tissues can be comparable to volumetric growth rates. Our study provides insight on how the biophysical properties of the tumor and host microenvironment, mechanical feedback control and diffusion-limited differential growth act in concert to regulate spatial patterns of stress and growth. When the tumor is stiffer than the host, our model predicts tumors are more able to change their size and mechanical state autonomously, which may help to explain why increased tumor stiffness is an established hallmark of malignant tumors.<br />Author summary The mechanical state of cells can modulate their growth and division dynamics via mechanotransduction, which affects both the cell size distribution and the tissue size as a whole. Experiments on tumor spheroids have shown that compressive stress from their environment can reversibly decrease tumor expansion rates and final sizes. Besides external confinement and compression on the tumor border, a heterogeneous stress field can be generated inside the tumor by nutrient-driven differential growth. Such growth-induced mechanical stresses can be relaxed by tissue rearrangement, which happens during cell neighbor exchanges, cell divisions, and extracellular matrix renewal. In this study, we have developed a continuum model that describes the above mechanical interactions and the dynamics of tissue rearrangement explicitly. Motivated by published experimental data, we consider mechanotransduction where the local compressive stress slows down cell growth and cell size reduction limits cell division. We have analyzed how external mechanical stimuli and internal processes influence the outcome of cell-and-tissue sizes and spatial patterns of cell density and mechanical stress in growing tumors.
- Subjects :
- 01 natural sciences
0302 clinical medicine
Neoplasms
Tumor Cells, Cultured
Stress relaxation
Medicine and Health Sciences
Cell Cycle and Cell Division
Biology (General)
Anisotropy
0303 health sciences
Ecology
Physics
Compression
Stiffness
Classical Mechanics
Mechanics
Biomechanical Phenomena
Computational Theory and Mathematics
Oncology
Cell Processes
Modeling and Simulation
Physical Sciences
Mechanical Stress
medicine.symptom
Research Article
Materials science
QH301-705.5
Materials Science
Material Properties
Geometry
Viscoelasticity
Stress (mechanics)
Cellular and Molecular Neuroscience
03 medical and health sciences
Malignant Tumors
Position (vector)
Cell Line, Tumor
Spheroids, Cellular
0103 physical sciences
Genetics
medicine
Tumor Expansion
Humans
010306 general physics
Molecular Biology
Relaxation (Physics)
Ecology, Evolution, Behavior and Systematics
Cell Proliferation
030304 developmental biology
Computational Biology
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
Elasticity
Radii
Relaxation (physics)
Stress, Mechanical
030217 neurology & neurosurgery
Mathematics
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 17
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....5542913625cfdf8417ee81a0e02fb593