scholarly journals Sensing Traction Force on Matrix Induces Cell-Cell Distant Mechanical Communications for Self-assembly

2019 ◽  
Author(s):  
Mingxing Ouyang ◽  
Zhili Qian ◽  
Bing Bu ◽  
Yang Jin ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Long Range ◽  
Self Assembly ◽  
Cancer Metastasis ◽  
Traction Force ◽  
Airway Smooth Muscle Cells ◽  
Type I ◽  
Force Transmission ◽  
Biomechanical Force ◽  
The Matrix ◽  
Cell Cell

AbstractThe long-range biomechanical force propagating across large scale may reserve the capability to trigger coordinative responses within cell population such as during angiogenesis, epithelial tubulogenesis, and cancer metastasis. How cells communicate in a distant manner within the group for self-assembly remains largely unknown. Here we found that airway smooth muscle cells (ASMCs) rapidly self-assembled into well-constructed network on 3D Matrigel containing type I collagen (COL), which relied on long-range biomechanical force across the matrix to direct cell-cell distant interactions. Similar results happened by HUVEC cells to mimic angiogenesis. Interestingly, single ASMCs initiated multiple extended protrusions precisely pointing to neighboring cells in distance, depending on traction force sensing. Separate ASMCs sensed each other to move directionally on both non-fibrous Matrigel and more efficiently when containing fibrous COL, but lost mutual sensing on fixed gel or coated glass due to no long-range force transmission. Beads tracking assay demonstrated distant transmission of traction force, and finite element method modeling confirmed the consistency between maximum strain distribution on matrix and cell directional movements in experiments. Furthermore, ASMCs recruited COL from the hydrogel to build fibrous network to mechanically stabilize cell network. Our results revealed for the first time that cells can sense traction force transmitted through the matrix to initiate cell-cell distant mechanical communications, resulting in cell directional migration and coordinative self-assembly with active matrix remodeling. As an interesting phenomenon, cells sound able to ‘make phone call’ via long-range biomechanics, which implicates physiological importance such as for tissue pattern formation.

scholarly journals Sensing Traction Force on the Matrix Induces Cell–Cell Distant Mechanical Communications for Self-Assembly

2020 ◽  
Vol 6 (10) ◽  
pp. 5833-5848
Author(s):  
Mingxing Ouyang ◽  
Zhili Qian ◽  
Bing Bu ◽  
Yang Jin ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Self Assembly ◽  
Traction Force ◽  
The Matrix ◽  
Cell Cell

scholarly journals Force localization modes in dynamic epithelial colonies

2018 ◽  
Vol 29 (23) ◽  
pp. 2835-2847 ◽  
Author(s):  
Erik N. Schaumann ◽  
Michael F. Staddon ◽  
Margaret L. Gardel ◽  
Shiladitya Banerjee
Keyword(s):  
Cancer Metastasis ◽  
Wide Spectrum ◽  
Traction Force ◽  
Cellular Motility ◽  
Force Transmission ◽  
Mechanical Coupling ◽  
Cell Behaviors ◽  
Force Dynamics ◽  
Epithelial Tissues ◽  
Cell Matrix Interactions

Collective cell behaviors, including tissue remodeling, morphogenesis, and cancer metastasis, rely on dynamics among cells, their neighbors, and the extracellular matrix. The lack of quantitative models precludes understanding of how cell–cell and cell–matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modeling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an active adherent vertex model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.

scholarly journals Force localization modes in dynamic epithelial colonies

2018 ◽  
Author(s):  
Erik N. Schaumann ◽  
Michael F. Staddon ◽  
Margaret L. Gardel ◽  
Shiladitya Banerjee
Keyword(s):  
Cancer Metastasis ◽  
Wide Spectrum ◽  
Computational Modelling ◽  
Traction Force ◽  
Cellular Motility ◽  
Force Transmission ◽  
Mechanical Coupling ◽  
Cell Behaviors ◽  
Force Dynamics ◽  
Epithelial Tissues

AbstractCollective cell behaviors, including tissue remodeling, morphogenesis and cancer metastasis rely on dynamics between cells, their neighbors and the extracellular matrix. The lack of quantitative models precludes understanding of how cell-cell and cell-matrix interactions regulate tissue-scale force transmission to guide morphogenic processes. We integrate biophysical measurements on model epithelial tissues and computational modelling to explore how cell-level dynamics alter mechanical stress organization at multicellular scales. We show that traction stress distribution in epithelial colonies can vary widely for identical geometries. For colonies with peripheral localization of traction stresses, we recapitulate previously described mechanical behavior of cohesive tissues with a continuum model. By contrast, highly motile cells within colonies produce traction stresses that fluctuate in space and time. To predict the traction force dynamics, we introduce an Active Adherent Vertex Model (AAVM) for epithelial monolayers. AAVM predicts that increased cellular motility and reduced intercellular mechanical coupling localize traction stresses in the colony interior, in agreement with our experimental data. Furthermore, the model captures a wide spectrum of localized stress production modes that arise from individual cell activities including cell division, rotation, and polarized migration. This approach provides a robust quantitative framework to study how cell-scale dynamics influence force transmission in epithelial tissues.

scholarly journals α-catenin facilitates mechanosensing and rigidity-dependent growth by linking integrin adhesions to F-actin

2021 ◽  
Author(s):  
Abhishek Mukherjee ◽  
Elisabeth Nadjar-Boger ◽  
Michael P. Sheetz ◽  
Haguy Wolfenson
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Force Transmission ◽  
Mesenchymal Transition ◽  
Cell Edge ◽  
Cell Matrix ◽  
The Matrix ◽  
Cell Adhesions ◽  
Dependent Growth ◽  
And Function ◽  
Cell Cell

AbstractThe physical interactions of cells with their external environment are critical for their survival and function. These interactions are altered upon epithelial to mesenchymal transition (EMT) as cells switch from relying primarily on cell-cell adhesions to relying on cell-matrix adhesions. Mechanical signals are central to regulating these two types of interactions, but the crosstalk and the mechanobiological processes that mediate the transition between them are poorly understood. Here we show that α-catenin, a mechanosensitive protein that regulates cadherin-based cell-cell adhesions, directly interacts with integrin adhesions and regulates their growth as well as their transmission of mechanical forces into the matrix. In mesenchymal cells, α-catenin is recruited to the cell edge where it interacts with actin in regions devoid of α-actinin. As actin and α-catenin flow from the cell edge toward the center, α-catenin interacts with vinculin within integrin adhesions to mediate adhesion maturation, enhance force transmission, and drive the proper assembly of actin stress fibers. Importantly, in the absence of α-catenin–vinculin interactions, cell adhesion to the matrix is impaired, and the cells display aberrant responses to matrix rigidity which is manifested in rigidity-independent growth. These results provide a novel understanding of α-catenin as having a dual-role in mechanosensing by both cell-cell and cell-matrix adhesions.

Anti-Twinning in an Ni-Mo-Cr Alloy

2013 ◽  
Vol 203-204 ◽  
pp. 254-257
Author(s):  
Mirosław Wróbel ◽  
Elżbieta Stępniowska ◽  
Stanisław Dymek
Keyword(s):  
Long Range ◽  
The Body ◽  
Type I ◽  
Face Centered Cubic ◽  
The Matrix ◽  
The Face ◽  
Face Centered ◽  
Long Range Ordering ◽  
Mechanical Twins ◽  
Crystallographic Orientations

Two morphological types of mechanical twins occur in the microstructure of cold rolled Ni-Mo-Cr alloy: long – passing over whole grains and micro-twins – confined to individual long range ordered domains. Long mechanical twins were only formed in the disordered alloy. Such twins are typical for metals with the face centered cubic structure with relatively low stacking fault energy. They do not form in the grains with twinning prohibited crystallographic orientations, e.g. {110}. Both types of twins were found in an alloy subjected to prolong annealing at 650 °C. The annealing induces long range ordering reaction leading to the formation of ordered domains with the body centered orthorombic crystal structure (oI8). The twins were of type I, type II, compound twins or pseudo-twins, depending on the crystallographic orientation of the ordered phase in relation to the matrix. It was found that twins of such types were formed even in grains with the {110} orientation and result from the anti-twinning deformation. However, in this orientation they were confined to ordered domains rather than developed into the long form crossing entire grains. On the other hand, the long twins of various types were formed in grains with other twinning favoring crystallographic orientations.

scholarly journals Recovery of Tractions Exerted by Single Cells in Three-Dimensional Nonlinear Matrices

2020 ◽  
Vol 142 (8) ◽  
Author(s):  
Dawei Song ◽  
Li Dong ◽  
Mukund Gupta ◽  
Linqing Li ◽  
Ottmar Klaas ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Single Cells ◽  
Three Dimensional ◽  
Traction Force ◽  
Simulated Data ◽  
Nonlinear Effects ◽  
Stem Cell Differentiation ◽  
Large Strains ◽  
The Matrix ◽  
Minimization Procedure

Abstract Cell-generated tractions play an important role in various physiological and pathological processes such as stem-cell differentiation, cell migration, wound healing, and cancer metastasis. Traction force microscopy (TFM) is a technique for quantifying cellular tractions during cell–matrix interactions. Most applications of this technique have heretofore assumed that the matrix surrounding the cells is linear elastic and undergoes infinitesimal strains, but recent experiments have shown that the traction-induced strains can be large (e.g., more than 50%). In this paper, we propose a novel three-dimensional (3D) TFM approach that consistently accounts for both the geometric nonlinearity introduced by large strains in the matrix, and the material nonlinearity due to strain-stiffening of the matrix. In particular, we pose the TFM problem as a nonlinear inverse hyperelasticity problem in the stressed configuration of the matrix, with the objective of determining the cellular tractions that are consistent with the measured displacement field in the matrix. We formulate the inverse problem as a constrained minimization problem and develop an efficient adjoint-based minimization procedure to solve it. We first validate our approach using simulated data, and quantify its sensitivity to noise. We then employ the new approach to recover tractions exerted by NIH 3T3 cells fully encapsulated in hydrogel matrices of varying stiffness. We find that neglecting nonlinear effects can induce significant errors in traction reconstructions. We also find that cellular tractions roughly increase with gel stiffness, while the strain energy appears to saturate.

Abstract 308: An in vitro Model of Cardiac Stem Cell Therapy to Study the Coupling of Primary and Stem Cell-derived Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Francesco S Pasqualini ◽  
Yvonne Aratyn-Schaus ◽  
Hongyan Yuan ◽  
Megan L McCain ◽  
George J Ye ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Cardiac Myocytes ◽  
Traction Force ◽  
Cardiac Cell ◽  
Force Transmission ◽  
Cardiac Cell Therapy ◽  
Cell Cell

For cardiac cell therapy to be effective, newly formed immature cardiomyocytes need to structurally and functionally integrate with the existing myocardium. Unfortunately, testing the electro-chemo-mechanical coupling of mature and immature cardiomyocytes in vivo is difficult. Here we engineered two cell μtissues containing combinations of mouse neonate, ES-derived, and iPS-derived cardiac myocytes on flexible substrates and utilized ratiometric calcium detection and traction force microscopy to measure excitation-contraction coupling in individual cells and in the pairs. We found that SC-derived cardiac myocytes can structurally couple with neonate cardiomyocytes to functionally support synchronous contraction, yet diastolic calcium levels were reduced in SC-derived cardiomyocytes. Consistently, neonate cardiomyocytes exerted peak systolic forces that were ~1.5-fold higher than that generated by SC-derived myocytes, yielding an imbalance in tension within the pair that was dissipated by focal adhesion-like structures at the cell-cell boundary. Finally we developed a finite element model of two-cell tissue contraction to demonstrate that an imbalance in isometric tension is sufficient to limit force transmission across cell-cell boundaries. Taken together, these results suggest that reduced force transmission between poorly coupled immature and native cardiomyocytes may explain the incomplete repair of ejection fraction observed in several clinical studies of cardiac cell therapy.

scholarly journals Glycosaminoglycans Modulate Long-Range Mechanical Communication Between Cells in Collagen Networks

2021 ◽  
Author(s):  
Xingyu Chen ◽  
Dongning Chen ◽  
Ehsan Ban ◽  
Paul A. Janmey ◽  
Rebecca G. Wells ◽  
...  
Keyword(s):  
Long Range ◽  
Collagen Fiber ◽  
Cancer Metastasis ◽  
Cell Communication ◽  
Swelling Pressure ◽  
Collagen Fibers ◽  
Collagen Gels ◽  
Force Transmission ◽  
Fiber Alignment ◽  
Collagen Fiber Alignment

AbstractCells can sense and respond to mechanical forces in fibrous extracellular matrices (ECM) over distances much greater than their size. This phenomenon, termed long-range force transmission, is enabled by the realignment (buckling) of collagen fibers along directions where the forces are tensile (compressive). However, whether other key structural components of the ECM, in particular glycosaminoglycans (GAGs), can affect the efficiency of cellular force transmission remains unclear. Here we developed a theoretical model of force transmission in collagen networks with interpenetrating GAGs, capturing the competition between tension-driven collagen-fiber alignment and the swelling pressure induced by GAGs. Using this model, we show that the swelling pressure provided by GAGs increases the stiffness of the collagen network by stretching the fibers in an isotropic manner. We found that the GAG-induced swelling pressure can help collagen fibers resist buckling as the cells exert contractile forces. This mechanism impedes the alignment of collagen fibers and decreases long-range cellular mechanical communication. We experimentally validated the theoretical predictions by comparing collagen fiber alignment between cellular spheroids cultured on collagen gels versus collagen-GAG co-gels. We found significantly less alignment of collagen in collagen-GAG co-gels, consistent with the prediction that GAGs can prevent collagen fiber alignment. The roles of GAGs in modulating force transmission uncovered in this work can be extended to understand pathological processes such as the formation of fibrotic scars and cancer metastasis, where cells communicate in the presence of abnormally high concentrations of GAGs.Statement of significanceGlycosaminoglycans (GAGs) are carbohydrates that are expressed ubiquitously in the human body and are among the key macromolecules that influence development, homeostasis, and pathology of native tissues. Abnormal accumulation of GAGs has been observed in metabolic disorders, solid tumors, and fibrotic tissues. Here we theoretically and experimentally show that tissue swelling caused by the highly polar nature of GAGs significantly affects the mechanical interactions between resident cells by altering the organization and alignment of the collagenous extracellular matrix. The roles of GAGs in modulating cellular force transmission revealed here can guide the design of biomaterial scaffolds in regenerative medicine and provides insights on the role of cell-cell communication in tumor progression and fibrosis.

scholarly journals Extracellular matrix stiffness regulates force transmission pathways in multicellular ensembles of human airway smooth muscle cells

2018 ◽  
Author(s):  
Samuel R. Polio ◽  
Suzanne E Stasiak ◽  
Ramaswamy Krishnan ◽  
Harikrishnan Parameswaran
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Focal Adhesions ◽  
Critical Factor ◽  
Fluorescent Imaging ◽  
Airway Smooth Muscle Cells ◽  
Force Transmission ◽  
Transmission Pathways ◽  
Cell Ensemble ◽  
Cell Cell

AbstractFor an airway or a blood vessel to narrow, there must be a connected path that links the smooth muscle (SM) cells with each other, and transmits forces around the organ, causing it to constrict. Currently, we know very little about the mechanisms that regulate force transmission pathways in a multicellular SM ensemble. Here, we used extracellular matrix (ECM) micropatterning to study force transmission in a two-cell ensemble of SM cells. Using the two-SM cell ensemble, we demonstrate (a) that ECM stiffness acts as a switch that regulates whether SM force is transmitted through the ECM or through cell-cell connections. (b) Fluorescent imaging for adherens junctions and focal adhesions show the progressive loss of cell-cell borders and the appearance of focal adhesions with the increase in ECM stiffness (confirming our mechanical measurements). (c) At the same ECM stiffness, we show that the presence of a cell-cell border substantially decreases the overall contractility of the SM cell ensemble. Our results demonstrate that connectivity among SM cells is a critical factor to consider in the development of diseases such as asthma and hypertension.

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