scholarly journals Stress generation, relaxation and size control in confined tumor growth

2021 ◽  
Vol 17 (12) ◽  
pp. e1009701
Author(s):  
Huaming Yan ◽  
Daniel Ramirez-Guerrero ◽  
John Lowengrub ◽  
Min Wu
Keyword(s):  
Stress Relaxation ◽  
Cell Density ◽  
Malignant Tumors ◽  
Size Control ◽  
Stress Generation ◽  
Current Position ◽  
Volumetric Growth ◽  
Differential Growth ◽  
Elastic Stresses ◽  
Control Feedback

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.

scholarly journals Stress generation, relaxation and size control in confined tumor growth

2019 ◽  
Author(s):  
H. Yan ◽  
D. Ramirez-Guerrero ◽  
J. Lowengrub ◽  
M. Wu
Keyword(s):  
Stress Relaxation ◽  
Malignant Tumors ◽  
Size Control ◽  
Maxwell Model ◽  
Stress Generation ◽  
Current Position ◽  
Volumetric Growth ◽  
Differential Growth ◽  
Elastic Stresses ◽  
Mechanical Feedback

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 letter, we present a new continuum model to investigate how the instantaneous elastic moduli and active stress relaxation, in conjunction with mechanical feedback machinery within cells, regulate the sizes of and stress distributions within growing tumors 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. By fitting the model to experimental data from two independent studies of tumor spheroid growth, 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.PACS numbers: 46.15.Cc,62.20.mt,68.55.at,87.19.1x,87.19.R-

Cell proliferation in the gastrulating chick embryo: a study using BrdU incorporation and PCNA localization

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 389-399 ◽  
Author(s):  
E.J. Sanders ◽  
M. Varedi ◽  
A.S. French
Keyword(s):  
Cell Proliferation ◽  
Chick Embryo ◽  
Cell Density ◽  
Generation Time ◽  
Primitive Streak ◽  
S Phase ◽  
Nuclear Antigen ◽  
Brdu Incorporation ◽  
Similar Proportion ◽  
Differential Growth

Cell proliferation in the gastrulating chick embryo was assessed using two independent techniques which mark cells in S phase of the mitotic cycle: nuclear incorporation of bromodeoxyuridine (BrdU) detected immunocytochemically and immunolocalization of proliferating cell nuclear antigen (PCNA). Computer-reconstructed maps were produced showing the distribution of labelled nuclei in the primitive streak and the cell layers. These distributions were also normalized to take into account regional differences in cell density across the embryo. Results from a 2 hour pulse of BrdU indicated that although cells at caudal levels of the primitive streak showed the highest incorporation, this region showed a similar proportion of labelled cells to the surrounding caudal regions of the epiblast and mesoderm when normalized for cell density. The entire caudal third of the embryo showed the highest proportion of cells in S phase. Cells of Hensen's node showed a relatively low rate of incorporation and, although the chordamesoderm cells showed many labelled nuclei, this appeared to be a reflection of a high cell density in this region. Combining this result with results from a 4 hour pulse of BrdU permitted mapping of cell generation time across the entire embryo. Generation times ranged from a low value of approximately 2 hours at caudal levels of both the epiblast and mesoderm, to an upper value of approximately 10 hours in the rostral regions of the primitive streak, in the mid-lateral levels of the epiblast and in the chordamesoderm rostral to Hensen's node. Cells at caudal regions of the primitive streak showed a generation time of approximately 5 hours. Taking into account that cells are generally considered to be continuously moving through the primitive streak, we conclude that cell division, as judged by generation time, is greatly reduced during transit through this region, despite the presence there of cells in S phase and M phase. Immunocytochemical localization of PCNA-positive nuclei gave generally similar distributions to those obtained with BrdU incorporation, confirming that this endogenous molecule is a useful S-phase marker during early embryogenesis. Mid-levels and caudal levels of the primitive streak showed the highest numbers of positive nuclei, and the highest proportion of labelling after cell density was accounted for. As with BrdU incorporation, the highest proportions of PCNA-positive nuclei were found towards the caudal regions of the epiblast and mesoderm. These results suggest that the differential growth of the caudal region of the embryo at this time is a direct consequence of elevated levels of cell proliferation in this region.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Xyloglucan Remodeling Defines Auxin-Dependent Differential Tissue Expansion in Plants

2021 ◽  
Vol 22 (17) ◽  
pp. 9222 ◽  
Author(s):  
Silvia Melina Velasquez ◽  
Xiaoyuan Guo ◽  
Marçal Gallemi ◽  
Bibek Aryal ◽  
Peter Venhuizen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Growth Control ◽  
Size Control ◽  
Tissue Expansion ◽  
Major Type ◽  
Hypocotyl Growth ◽  
Differential Growth ◽  
Rigid Cell Wall ◽  
Molecular Complexity ◽  
Genetic Interference

Size control is a fundamental question in biology, showing incremental complexity in plants, whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Our results indicate that auxin-reliant growth programs affect the molecular complexity of xyloglucans, the major type of cell wall hemicellulose in eudicots. Auxin-dependent induction and repression of growth coincide with reduced and enhanced molecular complexity of xyloglucans, respectively. In agreement with a proposed function in growth control, genetic interference with xyloglucan side decorations distinctly modulates auxin-dependent differential growth rates. Our work proposes that auxin-dependent growth programs have a spatially defined effect on xyloglucan’s molecular structure, which in turn affects cell wall mechanics and specifies differential, gravitropic hypocotyl growth.

Stress and Microstructural Evolution of Lpcvd Polysilicon Thin Films During High Temperature Annealing

1996 ◽  
Vol 441 ◽  
Author(s):  
Chia-Liang Yu ◽  
Paul A. Flinn ◽  
Seok-Hee Lee ◽  
John C. Bravman
Keyword(s):  
Thin Films ◽  
High Temperature ◽  
Stress Relaxation ◽  
Deposition Temperature ◽  
Stress Generation ◽  
Deformation Model ◽  
Silicon Thin Films ◽  
Compressive Stresses ◽  
Polysilicon Films ◽  
Curvature Measurements

AbstractThe mechanisms of stress generation and stress relaxation of LPCVD silicon thin films were studied using high temperature wafer curvature measurements. The stresses generated during depositions are measured as functions of deposition temperature and microstructure. Amorphous silicon deposited with a compressive stress shows a large stress change toward tensile during crystallization. The stress relaxation of polysilicon films deposited with tensile stresses can be described by a deformation model from Ashby and Frost [1]. The polysilicon films deposited with compressive stresses have hydrogen incorporated during deposition and shows hydrogen evolution during thermal cycles.

scholarly journals Volumetric finite-element modelling of biological growth

Open Biology ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 190057 ◽  
Author(s):  
Richard Kennaway ◽  
Enrico Coen
Keyword(s):  
Finite Element ◽  
Finite Element Modelling ◽  
Shape Change ◽  
Growth Patterns ◽  
Three Dimensions ◽  
Volumetric Growth ◽  
Differential Growth ◽  
Element Modelling ◽  
Wide Range ◽  
Polarity Field

Differential growth is the driver of tissue morphogenesis in plants, and also plays a fundamental role in animal development. Although the contributions of growth to shape change have been captured through modelling tissue sheets or isotropic volumes, a framework for modelling both isotropic and anisotropic volumetric growth in three dimensions over large changes in size and shape has been lacking. Here, we describe an approach based on finite-element modelling of continuous volumetric structures, and apply it to a range of forms and growth patterns, providing mathematical validation for examples that admit analytic solution. We show that a major difference between sheet and bulk tissues is that the growth of bulk tissue is more constrained, reducing the possibility of tissue conflict resolution through deformations such as buckling. Tissue sheets or cylinders may be generated from bulk shapes through anisotropic specified growth, oriented by a polarity field. A second polarity field, orthogonal to the first, allows sheets with varying lengths and widths to be generated, as illustrated by the wide range of leaf shapes observed in nature. The framework we describe thus provides a key tool for developing hypotheses for plant morphogenesis and is also applicable to other tissues that deform through differential growth or contraction.

scholarly journals Xyloglucan remodelling defines differential tissue expansion in plants

2019 ◽  
Author(s):  
Silvia Melina Velasquez ◽  
Xiaoyuan Guo ◽  
Marçal Gallemi ◽  
Bibek Aryal ◽  
Peter Venhuizen ◽  
...  
Keyword(s):  
Cell Wall ◽  
Growth Control ◽  
Size Control ◽  
Tissue Expansion ◽  
Central Importance ◽  
Hypocotyl Growth ◽  
Differential Growth ◽  
Rigid Cell Wall ◽  
Genetic Interference ◽  
Cell Wall Mechanics

Size control is a fundamental question in biology, showing incremental complexity in case of plants whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Here we show that growth inducing and repressing auxin conditions correlate with reduced and enhanced complexity of extracellular xyloglucans, respectively. In agreement, genetic interference with xyloglucan complexity distinctly modulates auxin-dependent differential growth rates. Our work proposes that an auxin-dependent, spatially defined effect on xyloglucan structure and its effect on cell wall mechanics specify differential, gravitropic hypocotyl growth.

scholarly journals Self-organization of Tissue Growth by Interfacial Mechanical Interactions in Multi-layered Systems

2021 ◽  
Author(s):  
Tailin Chen ◽  
Yan Zhao ◽  
Xinbin Zhao ◽  
Shukai Li ◽  
Jialing Cao ◽  
...  
Keyword(s):  
Asymmetric Cell Division ◽  
Size Control ◽  
Tissue Growth ◽  
Cell Junction ◽  
Adhesion Forces ◽  
Layered Systems ◽  
Differential Growth ◽  
Cell Sheets ◽  
Self Organized ◽  
3D Deformation

Morphogenesis is a spatially and temporally regulated process involved in various physiological and pathological transformations. In addition to the associated biochemical factors, the physical regulation of morphogenesis has attracted increasing attention. However, the driving force of morphogenesis initiation remains elusive. Here, we show that during the growth of multi-layered tissues, morphogenetic process can be self-organized by the progression of compression gradient stemmed from the interfacial mechanical interactions between layers. In tissues with low fluidity, the compression gradient is progressively strengthened during differential growth between layers and induces stratification through triggering symmetric-to-asymmetric cell division reorientation at the critical tissue size. In tissues with higher fluidity, compression gradient is dynamic and induces 2D in-plane morphogenesis instead of 3D deformation accompanied with cell junction remodeling regulated cell rearrangement. Morphogenesis can be tuned by manipulating tissue fluidity, cell adhesion forces and mechanical properties to influence the progression of compression gradient during the development of cultured cell sheets and chicken embryos. Together, the progression of compression gradient regulated by interfacial mechanical interaction provides a conserved mechanism underlying morphogenesis initiation and size control during tissue growth.

scholarly journals Restructuring of emergent grain boundaries at free surfaces – an interplay between core stabilization and elastic stress generation

2022 ◽  
Author(s):  
Xiaopu Zhang ◽  
Mengyuan Wang ◽  
Hailong Wang ◽  
Moneesh Upmanyu ◽  
John Boland
Keyword(s):  
Grain Boundaries ◽  
Triple Junction ◽  
Elastic Stress ◽  
Stress Generation ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Free Surfaces ◽  
Core Stabilization ◽  
Elastic Stresses ◽  
Boundary Relaxation

Abstract Scanning tunneling microscopy and numerical calculations are used to study the structure and relaxation of grain boundaries at the surface of planar nanocrystalline copper (111) films and bicrystals. We show that the strong energetic preference for boundary cores to lie along close-packed planes introduces a restructuring that rotates adjoining grains and generates elastic stresses in the triple junction region. The interplay of this stress field and the core stabilization determines the length scale of the restructuring and controls the shape and magnitude of the displacement field around the triple junction. Depending on the in-plane angle, restructured boundaries can extend to depths of ~ 15 nm with the associated elastic stress fields extending to even greater depths. These results point to a new mechanism of boundary relaxation at surfaces that is expected to play an important role in grain coalescence and stress evolution in growing films.

Am80, a RARα Specific Synthetic Retinoid Induced a Strong Growth Inhibition in Hematologic Malignant Cells Including Myeloid and Lymphoid Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4438-4438
Author(s):  
Shiro Jimi ◽  
Kota Mashima ◽  
Mitsukuni Sakabe ◽  
Emiko Ushijima ◽  
Junji Suzumiya ◽  
...  
Keyword(s):  
Cell Death ◽  
Growth Inhibition ◽  
Cell Density ◽  
Cultured Cells ◽  
Malignant Tumors ◽  
Specific Binding ◽  
Background Level ◽  
Cell Number ◽  
Dead Cell ◽  
Strong Growth

Abstract Acute promyelocytic leukemia (APL) is an objective disease for treatment with retinoids including ATRA, however adverse effects appear due to non-specific binding to different retinoic acid receptors (RARs). To overcome this disadvantage a targeting drug namely Am-80, Tamibarotene, has been developed, which can react specifically to RARα. On the other hand, recent studies addressed that other therapeutic applications with retinoids can be use against malignant tumors other than APL. Therefore the mechanisms of selective action of Am-80 on tumor cells were still obscure. In the present study, we studied effects of Am-80 regarding cell death and growth inhibition using myeloid and lymphoid malignant cultured cells, i.e., HL60, HL60R, K-562, Kasumi-1, MEG01, Raji, U266B1, and U937. Expression of RARs was analyzed by a FACS-based GUAVA PCA method using 3 sets of cell samples [1st antibody (−)/2nd PE-antibody (−), (−/+), (+/+)], then median value of fluorescence intensity was obtained and calculated a relative expression value with following formula: ((+/+)-((−/+)-(−/−)))/(−/−), by which each tumor cell with different background level can be standardized. In normal growing condition, RARα in HL60 was significantly greater (p<0.006) than in not only HL60R but also all of other cells. Effects of Am-80 were examined on cell growth during 9 days of incubation with 0.5% ethanol and 10−7~−5 M Am-80 in ethanol. In this culture we always kept cells in an exponential growth by adjusting cell number to 5x105/10 ml/flask at the time of subculture in each 3-day-interval. All of the time points viable and dead cell number was monitored by FACS-based GUAVA ViaCount assay. HL-60 was found to be only a cell type sensitive to Am-80, by which viable cell density was reduced more than 95 % after 9 days of incubation. Dead/total cell density gradually increased after 3 days of incubation, and reached about 40 % after 9 days of incubation. Mode of cell death was examined by assessments for annexin V, intracellular dissociated-caspases and TUNEL, showing that most of dead cells were apoptotic cells, but necrotic cells appeared at a minimum level. Expression of RARα in HL60 with Am-80 decreased strongly during 9 days of incubation, and reached a level lower than that in HL60R. While, no change was found in HL60R during incubation with Am-80. Next, Am-80-inducing growth inhibition was examined. Growth inhibition was time- and dose-dependently occurred in all of the cells, and reached 40–70 % by 10−5 M Am-80 after 9 days of incubation. The growth inhibition value was negatively correlated with RARα expression value (r=−0.534, p=0.04). When TGFβ in cultures with different concentrations of Am-80 was quantified by an ELISA method, TGFβ was released dose-dependently, and its reactivity was negatively correlated with RARα expression value. These results indicated that Am-80-inducing strong growth inhibition was mediated by TGFβ in an autocrine manner, in which RARα pool size may be a regulatory factor.

Effect of lung lavage on the stress relaxation of the respiratory system

1993 ◽  
Vol 75 (4) ◽  
pp. 1536-1544 ◽  
Author(s):  
J. J. Perez Fontan
Keyword(s):  
Stress Relaxation ◽  
Respiratory System ◽  
Time Course ◽  
Lung Lavage ◽  
Elastic Recoil ◽  
Lung Inflation ◽  
Pressure Losses ◽  
Elastic Stresses ◽  
Double Exponential ◽  
Before And After

To test the hypothesis that lowering the concentrations of surfactant molecules at the gas-liquid interface increases viscoelastic dissipation in the lungs, the amplitude and time course of stress relaxation were quantified before and after lavage of the lungs with warm saline in five newborn and five 8-wk-old anesthetized piglets. Stress relaxation was separated from other dissipative pressure losses by fitting the pressure decays that follow airway occlusions performed during a period of constant inspiratory flow to a double-exponential regression. The amplitude of stress relaxation (defined by the term of the regression with the longest time constant) related linearly to the changes in respiratory system volume and elastic recoil preceding the occlusions both before and after the lavage. Lung lavage increased the slope of both relationships without altering the time course of the relaxations. In addition to being consistent with the proposed hypothesis, these results suggest that viscoelastic pressure losses remain linked to the elastic stresses generated during lung inflation, as proposed by Fredberg and Stamenovic's structural dumping theory (J. Appl. Physiol. 67: 2408#x2013;2419, 1989).

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